Mitotic inhibitor - Knowledge

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leads to a change in the shape of P-gp and opens a channel through which the drug is pumped out of the cell. Hydrolysis of a second molecule of ATP results in closing of the channel and the cycle is repeated. P-glycoprotein has affinity to hydrophobic drugs with a positive charge or electrically neutral and is often over-expressed in many human cancers. Some tumors, e.g. lung cancer, do not over-express this transporter but also are able to develop the resistance. It was discovered that another transporter MRP1 also work as the efflux pump, but in this case substrates are negatively charged natural compounds or drugs modified by glutathione, conjugation, glycosylation, sulfation and glucuronylation. Drugs can enter into a cell in few kinds of ways. Major routes are: diffusion across the plasma membrane, through receptor or transporter or by the

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high concentrations. They induce mitotic arrest in the G2-M phase of the cell cycle, resulting in apoptosis. Epothilone A and epothilone B exhibit both antifungal and cytotoxic properties. These epothilones are competitive inhibitors of the binding of paclitaxel to tubulin, exhibiting activity at similar concentrations. This finding leads to assume that the epothilones and paclitaxel adopt similar conformations in vivo. However, the epothilones are around 30 times more water-soluble than paclitaxel and more available, being easily obtained by fermentation of the parent myxobacterium and could be prepared by total synthesis. The epothilones also shows not to be recognized by multidrug resistant mechanisms, therefore it has much higher potency than paclitaxel in multidrug resistant cell lines.

1876:. Cancer can develop the resistance by mutations to their cells which result in alterations in the surface of cells or in impaired endocytosis. Mutation can eliminate or change transporters or receptors which allows drugs to enter into the tumor cell. Other cause of drug resistance is a mutation in β tubulin which cause alterations in binding sites and a given drug cannot be bound to its target. Tumors also change expression isoforms of tubulin for these ones, which are not targets for antimitotic drugs e.g. overexpress βIII-tubulin. In addition tumor cells express other kinds of proteins and change microtubule dynamic to counteract effect of anticancer drugs. Drug resistance can also develop due to the interruption in therapy. 465:

group increased the binding ability whereas the 1-methoxy group helped in attaining the correct conformation of the molecule. The stability of the tropone ring and the position of the methoxy and carbonyl group are crucial for the binding ability of the compound. The 10-methoxy group can be replaced with halogen, alkyl, alkoxy or amino groups without affecting tubulin binding affinity, while bulky substituents reduce the activity. Ring B when expanded showed reduced activity, however the ring and its C-7 side chain is thought to affect the conformation of the colchicine analogues rather than their tubulin binding ability. Substitution at C-5 resulted in loss of activity whereas attachment of annulated

1506:—used to treat breast cancer and non-small-cell lung cancer. It was developed under the direction of the French pharmacist Pierre Poiter, who, in 1989, obtained an initial license for the dug under the brand name Navelbine. Vinorelbine is also known as vinorelbine tartrate, the drug is a semi-synthetic analogue of another cancer-fighting drug, vinblastine. Vinorelbine is included in the class of pharmaceuticals known as vinca alkaloids, and many of its characteristics mimic the chemistry and biological mechanisms of the cytotoxic drugs vincristine and vinblastine. Vinorelbine showed promising activity against breast cancer and is in clinical trial for the treatment of other types of tumors. 404:

microtubule directly. They do not first form a complex with the soluble tubulin nor do they copolymerize to form the microtubule, however they are capable of bringing about a conformational change in tubulin in connection with tubulin self-association. Vinca alkaloids bind to the tubulin with high affinity at the microtubule ends but with low affinity at the tubulin sites present along the sides of the microtubule cylinder. The binding of these drugs at the high affinity sites results in strong kinetic suppression of tubulin exchange even at low drug concentration while their binding to the low affinity sites in relatively high drug concentration depolymerizes microtubules.

2000:) or shut down existing ones. Tumor cells die very fast after cutting off the oxygen supply what suggest these agents are especially interesting. What more, it seems the agents act only with tumor vasculature and do not interact with normal tissues. The mechanisms is not known but has been suggested that the reason are differences between young tissue of tumor and mature tissue of normal vasculature. Antivascular agents are similar to colchicine and bind to the colchicine binding site on β-tubulin so development of novel agents acting with colchicine binding site (which is not used by any of currently approved drugs) seems to be a promising approach. 284:'. Dynamic instability is a process in which the microtubule ends switches between periods of growth and shortening. The two ends are not equal, the α-tubulin ringed (-)end is less dynamic while the more dynamic β-tubulin ringed (+) end grows and shortens more rapidly. Microtubule undergoes long periods of slow lengthening, brief periods of rapid shortening and also a pause in which there is neither growth nor shortening. Dynamic instability is characterized by four variables: the rate of microtubule growth; the rate of shortening; frequency of transition from the growth or paused state to shortening (called a ' 1649:. Halichondrin B is a complex polyether macrolide which is synthesized and arrests cell growth at subnanomolar concentrations. Halichondrin B is noncompetitive inhibitor of the binding of both vincristine and vinblastine to tubulin, suggesting the drugs bind to the vinca binding site, or a site nearby. The isolation of halichondrin B is from two unrelated genera of sponge, has led to speculate that halichondrin B is a microbial in reality, rather than sponge metabolite because sponges support a wide range of microbes. If this is the case, fermentation technologies could provide a useful supply of halichondrin B. 1472:. The most interesting thing was that vinblastine and vincristine, were found to lower the number of white cells in blood. A high number of white cells in the blood indicates leukemia, so a new anti-cancer drug had been discovered. These two alkaloids bind to tubulin to prevent the cell from making the spindles that it needs to be able to divide. This is different from the action of taxol which interferes with cell division by keeping the spindles from being broken down. Vinblastine is mainly useful for treating 2027: 705: 1198: 717: 477: 446: 183: 383: 693: 1283: 1257: 528: 1224: 1184: 1468:. Madagascar traditionally used the vinca rosea to treat diabetes. In fact it has been used for centuries throughout the world to treat all kinds of ailments from wasp stings in India, to eye infections in the Caribbean. In the 1950s researchers began to analyse the plant and discovered that it contained over 70 alkaloids. Some were found to have effect on lower blood sugar levels and others act as 1094: 1191: 1101: 1290: 1165: 1141: 1778:μM. The drug, a macrolide (polyhydroxylated lactone), is a member of a structural diverse class of compounds called polyketides with notable chemical mechanism of action. It stabilizes the microtubules of target cells, essentially arresting them at a specific stage in the cell cycle and halting cell division. It is a promising marine-derived candidate for treating certain cancers. 1134: 1127: 371:. They decrease the microtubule polymer mass in the cells at high concentration and act as microtubule-destabilizing agents. The other class of inhibitors operate by inhibiting the depolymerization of polymerized tubulin and increases the microtubule polymer mass in the cells. They act as microtubule-stabilizing agents and are called depolymerization inhibitors like the 1392: 1061: 1054: 1047: 1087: 1724:, is a semi-synthetic analogue of paclitaxel, with a trade name Taxotere. Docetaxel has the minimal structure modifications at C13 side chain and C10 substitution showed more water solubility and more potency than paclitaxel. Clinical trials have shown that patients who develop hypersensitivity to paclitaxel may receive docetaxel without an allergic response. 1243: 1250: 33: 2011:

to polymer. In addition, use of water-soluble polymers allow hydrophilic anticancer agents become soluble. The nature of polymer-drug linkage can be designed to be stable in normal tissues and break down in tumor environment, which is more acidic. This approach allow for release active agent exactly in the target.

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Therapy with combination of two or more drugs which have various binding sites and/or different mechanism of action but have non overlapping adverse effects. This would allow use of drugs in low concentration what reduce strength of side effects associated with high doses of anticancer agents. Better

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and polymer-bound drugs comprise promising improvements in delivery system. Liposomes allow for delivery considerable amounts of drag to the tumor without toxic effect in normal tissues and slowly release drugs what result in prolongation of pharmaceutical action. Similar properties have drugs bound

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Nutt. (Taxaceae). Later it was also isolated from hazelnut trees (leaves, twigs, and nuts) and the fungi living on these trees but the concentration is only around 10% of the concentration in yew trees. Paclitaxel is also known as Taxol and Onxol to be an anti-cancer drug. The drug is the first line

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at subnanomolar concentrations. The peptides of dolastatins 10 and 15 noncompetitively inhibit the binding of vincristine to tubulin. Dolastatin 10 is 9 times more potent than dolastatin 15 and both are more potent than vinblastin. The dolastatins also enhance and stabilize the binding of colchicine

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other therapies. Colchicine is known to inhibit cell division and proliferation. Early study demonstrated that colchicine disrupts the mitotic spindle. Dissolution of microtubules subsequently was shown to be responsible for the effect of colchicine on the mitotic spindle and cellular proliferation.

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Colchicine is an anti-inflammatory drug that has been in continuous use for more than 3000 years. Colchicine is an oral drug, known to be used for treating acute gout and preventing acute attacks of familial Mediterranean fever (FMF). However, the use of colchicine is limited by its high toxicity in

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that of the GTP nucleotide along with some important differences. GTP binds at one end of the tubulin dimer keeping contact with the next dimer along each of the protofilament while the paclitaxel binds to one side of β-tubulin keeping contact with the next protofilament. GTP binds to unassembled

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after administration equal dose of a drug and different tolerance to effect of chemotherapy agents. The second problem is particularly important in treatment elderly people. Their body is weaker and need to apply lower doses, often below therapeutic level. Another problem with anticancer agents is

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showing highly potent cytotoxic activity. Cryptophycin 52 was originally developed as a fungicide, but was too toxic for clinical use. Later the research was focused on treating cryptophycin as a microtubule poison, preventing the formation of the mitotic spindle. Cryptophycin 52 showed high potent

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is a novel fluorinated vinca alkaloid currently in Phase II clinical trials, which in preclinical studies exhibited superior antitumor activity to vinorelbine and vinblastine. Vinflunine block mitosis at the metaphase/anaphase transition, leading to apoptosis. Vinflunine is a chemotherapy drug used

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material by analysis of G-Banded chromosomes, uses mitotic inhibitors extensively. In order to prepare a slide for cytogenetic study, a mitotic inhibitor is added to the cells being studied. This stops the cells during mitosis, while the chromosomes are still visible. Once the cells are centrifuged

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is the most important limitation in anticancer therapy. It can develop in many chemically distinct compounds. Until now, several mechanisms are known to develop the resistance. The most common is production of so-called "efflux pumps". The pumps remove drugs from tumor cells which lead to low drug

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The other dynamic behavior called treadmilling is the net growth of the microtubule at one end and the net shortening at the other end. It involves the intrinsic flow of tubulin sub-units from the plus end to the minus end. Both the dynamic behaviors are important and a particular microtubule may

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Because of numerous adverse effect and limitations in use, new drugs with better properties are needed. Especially are desired improvements in antitumor activity, toxicity profile, drug formulation and pharmacology. Currently have been suggested few approaches in development of novel therapeutic

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and is involved in moving nutrients and other biologically important compounds inside one cell or between cells. P-glycoprotein detects substrates when they enter the plasma membrane and bind them which causes activation of one of the ATP-binding domains. The next step is hydrolysis of ATP, which

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Limitations in anticancer therapy occur mainly due to two reasons; because of the patient's organism, or because of the specific genetic alterations in the tumor cells. From the patient, therapy is limited by poor absorption of a drug which can lead to low concentration of the active agent in the

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and it was found to be too toxic for use as an antifungal. Epothilones are microtubule stabilizing agents with a mechanism of action similar to taxanes, including suppression of microtubule dynamics, stabilization of microtubules, promotion of tubulin polymerization, and increased polymer mass at

499:. The importance of C-13 substituted phenylisoserine side chain to bioactivity of paclitaxel has been known for a long time. Several replacements at the C-3' substitution have been tested. Replacement of the C-3' phenyl group with alkyl or alkyneyl groups greatly enhanced the activity, and with CF 464:

ring (ring C) and a seven-membered ring (ring B) with an acetamido group located at its C-7 position. The trimethoxy phenyl group of colchicine not only helps in stabilizing the tubulin-colchicine complex but is also important for antitubulin activity in conjunction with the ring C. The 3-methoxy

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These protofilaments form the backbone of the hollow, cylindrical microtubule which is about 25 nanometers in diameter and varies from 200 nanometers to 25 micrometers in length. About 12–13 protofilaments arrange themselves in parallel to form a C-shaped protein sheet, which then curls around to

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E7010 is the most active of sulfonamide antimitotic agent, which has been shown to inhibit microtubule formation by binding at the site of colchicines. It is quite soluble in water as an acid salt. Methoxybenzene-sulfonamide showed good results against a wide range of tumor cells including vinca

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The Vinca alkaloids bind to the β-subunit of tubulin dimers at a distinct region called the Vinca-binding domain. They bind to tubulin rapidly, and this binding is reversible and independent of temperature (between 0 °C and 37 °C). In contrast to colchicine, vinca alkaloids bind to the

119:. Microtubules are created during normal cell functions by assembling (polymerizing) tubulin components, and are disassembled when they are no longer needed. One of the important functions of microtubules is to move and separate chromosomes and other components of the cell for cell division ( 260:(GDP). The stability of the microtubule will depend on whether the β-end is occupied by GTP or GDP. A microtubule having a GTP molecule at the β-end will be stable and continue to grow whereas a microtubule having a GDP molecule at the β-end will be unstable and will depolymerise rapidly. 1987:

Discovery agents which are not a substrate for efflux pump or modifications of drugs in toward lower affinity to transporting proteins. Discover P-glycoprotein inhibitors with higher affinity to the transporter then drugs, is next approach. For improving oral bioavailability is suggested

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Colchicine analogues blocks cell division by disrupting the microtubule. It has been reported that the β-subunit of tubulin is involved in colchicine binding. It binds to the soluble tubulin to form colchicine-tubulin complex. This complex along with the normal tubulins then undergoes

1704:(MDR) pump, a cellular pump which rapidly ejects foreign molecules from the cell. Combretastatin is also reported to be able to inhibit angiogenesis, a process essential for tumor growth. Except those factors, one of the disadvantage of combretastatin is the low water solubility. 1718:, binds to the colchicine site of tubulin, inducing the formation of abnormal microtubules. 2-Methoxyestradiol exhibits potent apoptotic activity against rapidly growing tumor cells. It also has antiangiogenic activity through a direct apoptotic effect on endothelial cells. 305: 1847:

their limited aqueous solubility what substantially reduces absorption of a drug. Problems with delivery of drags to the tumor occur also when active agent has high molecular weight which limits tissue penetration or the tumor has large volume prevent for penetration.

1741:. (Kaposi sarcoma is a cancer of the skin and mucous membranes that is commonly found in patients with acquired immunodeficiency syndrome, AIDS). It is so effective that some oncologists refer to the period before 1994 as the "pre-taxol" era for treating breast cancer. 355:

also, the microtubules attached to the chromosomes maintain a carefully regulated shortening and lengthening process. Thus the presence of a drug which can suppress the microtubule dynamics is sufficient to block the cell cycle and result in the death of the cells by

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antimitotic activity to resist spindle microtubule dynamics. As well, the interest in this drug has been further arose by the discovery that cryptophycin shows reduced susceptibility to the multidrug resistance pump, and shows no reduction of activity in a number of

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tube-shaped structure. The tubulin hetero-dimers arrange themselves in a head to tail manner with the α-subunit of one dimer coming in contact with the β-subunit of the other. This arrangement results in the formation of long protein fibres called protofilaments.

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to the resulting microtubule, which has an α-subunit at one end and a β-subunit at the other end. The α-tubulin end has negative (–) charges while the β-tubulin end has positive (+) charges. The microtubule grows from discrete assembly sites in the cells called

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One of the targets for anticancer drugs can be tumor vasculature. The advantage in this case is relatively easy access of therapeutic agents to the target. It is known that some compounds can inhibit the formation of new blood vessels (inhibit the process of

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because modification at C-16 and C-17 offers good opportunities for developing new analogues. The replacement of the ester group with an amide group at the C-16 resulted in the development of vindesine. Similarly replacement of the acetyl group at C-16 with

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Development of inhibitors that have their binding site in α-tubulin. This part of tubulin dimer remains unused because all currently use drugs bind to the β-tubulin. Research in this field can open new opportunity in treatment and provide new class of

107:, and prevent cells from undergoing mitosis by disrupting microtubule polymerization, thus preventing cancerous growth. Microtubules are long, ropelike proteins that extend through the cell and move cellular components around. Microtubules are long 659:

Tubulin binding molecules differ from the other anticancer drugs in their mode of action because they target the mitotic spindle and not the DNA. Tubulin binding drugs have been classified on the basis of their mode of action and binding site as:

1700:. Combretastatin is one of the simpler compounds to show antimitotic effects by interaction with the colchicine binding site of tubulin, and is also one of the most potent inhibitors of colchicine binding. Combretastatin is not recognized by the 554:

modification of vinblastine gave vinorelbine which shows comparable activity as that of vinblastine. Another analogue prepared was the difluoro derivative of vinorelbine which showed improved in vivo antitumor activity. It was discovered that

651:, they swell, spreading the chromosomes. After preparation, the chromosomes of the cells can be viewed under a microscope to have the banding patterns of the chromosomes examined. This experiment is crucial to many forms of cancer research. 507:

and epoxide moieties were also found to be potent. Most of the analogues without ring A were found to be much less active than paclitaxel itself. The analogues with amide side chain at C-13 are less active than their ester counterpart. Also

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gave rise to new analogues having anti- tubulin activity. Also it was found that the vindoline's indole methyl group is a useful position to functionalize potentially and develop new, potent vinblastine derivatives. A new series of

419:, and it reduces the critical tubulin sub-unit concentration (i.e., soluble tubulin concentration at steady- state). Microtubules polymerized in presence of paclitaxel are extremely stable. The binding mechanism of the paclitaxel 256:(GTP) are also important components of the microtubule structure. One molecule of GTP is tightly bound to the α-tubulin and is non-exchangeable whereas the other GTP molecule is bound to β-tubulin and can be easily exchanged with 1892:

Poor water solubility of drugs which need to be dissolved in polyoxyethylated castor oil or polysorbate what cause hypersensitivity reactions. It has been suggested this solvents can also reduce delivery of the drugs to target

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which blocks the tubulin dimers from further addition and thereby prevents the growth of the microtubule. As the T-C complex slows down the addition of new dimers, the microtubule disassembles due to structural imbalance or

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Neuropathy which is significant side effect can develop at any time in therapy and require an interruption of treatment. After symptoms have resolved therapy can be started again but the break allow tumor for develop of

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is a highly potent drug which also has serious side effects especially on the neurological system. Therefore, new synthetic analogues were developed with the goal of obtaining more efficient and less toxic drugs. The

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of α/β-tubulin heterodimers at both the ends. This dynamic behavior and resulting control over the length of the microtubule is vital to the proper functioning of the mitotic spindle in mitosis i.e., cell division.

367:) and shortening (depolymerization). One class of inhibitors operate by inhibiting polymerization of tubulin to form microtubules and are called polymerization inhibitors like the colchicine analogues and the 1973:

Yews trees are poor source of active agents that limited the development of taxanes for over 20 years until discover the way of synthesis. In December 1992 paclitaxel was approved to use in chemotherapy.

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of tubulin by paclitaxel results in permanent stabilization of the microtubule. Thus the suppression of microtubule dynamics was described to be the main cause of the inhibition of cell division and of

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cell line and inhibit cell division by binding to the vinca alkaloid site on tubulin. Hemiasterlin A and B exhibit stronger antiproliferative activities than both the vinca alkaloids and paclitaxel.

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Agents which act as inhibitors of tubulin, also act as inhibitors of cell division. A microtubule exists in a continuous dynamic state of growing and shortening by reversible association and

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was initially found to have immunosuppressive and antifungal activities. Discodermolide is a polyhydroxylated alketetraene lactone marine product, isolated from the Bahamian deep-sea sponge,

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is one of the oldest known antimitotic drugs and in the past years much research has been done in order to isolate or develop compounds having similar structure but high activity and less

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to treat advanced transitional cell bladder and urothelial tract cancer. It is also called Javlor. It is licensed for people who have already had cisplatin or carboplatin chemotherapy.

309: 2182: 1796:, a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs. 131:

when two sets of fully formed chromosomes are supposed to separate into daughter cells. Tubulin binding molecules have generated significant interest after the introduction of the

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blood and small amount delivery to the tumor. Low serum level of a drug can be also caused by rapid metabolism and excretion associated with affinity to intestinal or/and liver

1842:. Another reason is the instability and degradation of the drugs in gastro-intestinal environment. Serious problem is also variability between patients what causes different 2536:

Jordan, Allan; Hadfield, John A.; Lawrence, Nicholas J.; McGown, Alan T. (1998). "Tubulin as a target for anticancer drugs: Agents which interact with the mitotic spindle".

460:. This resulted in the discovery of a number of colchicine analogues. The structure of colchicine is made up of three rings, a trimethoxy benzene ring (ring A), a methoxy 3643: 546:

at C-20', C-16' and C-14' in the velbanamine portion are critical and inversion leads to loss of activity. The C-16' carboxymethyl group is important for activity since

1541:). It inhibits mitosis by inhibiting microtubule polymerization. While colchicine is not used to treat cancer in humans, it is commonly used to treat acute attacks of 3465:

Ivachtchenko, Alexandre; Kiselyov, Alex; Tkachenko, Sergey; Ivanenkov, Yan; Balakin, Konstantin (2007). "Novel Mitotic Targets and Their Small-Molecule Inhibitors".

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Saville, M. W.; Lietzau, J.; Pluda, J. M.; Wilson, W. H.; Humphrey, R. W.; Feigel, E.; Steinberg, S. M.; Broder, S.; Yarchoan, R.; Odom, J.; Feuerstein, I. (1995).

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group at that position in combination with modification of the 10-Ac with other acyl groups increased the activity several times. Another modification of C-3' with

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polymerization to form the microtubule. However the presence of this T-C complex prevents further polymerization of the microtubule . This complex brings about a

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Cragg, Gordon M.; Newman, David J. (2004). "A Tale of Two Tumor Targets: Topoisomerase I and Tubulin. The Wall and Wani Contribution to Cancer Chemotherapy†".

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b) Vinca alkaloids binding site, includes vinblastine, vincristine, vinorelbine, vinflunine, dolastatins, halichondrins, hemiasterlins, cryptophysin 52, etc.

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of eukaryotic cells and have an important role in various cellular functions such as intracellular migration and transport, cell shape maintenance, polarity,

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efficiency might be also a result of maintenance low concentrations of drugs for long period instead of drastic changes in the amount of administered drugs.

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C-16 -spiro-oxazolidine-1,3-diones prepared from 17-deacetyl vinblastine showed good anti-tubulin activity and lower cytotoxicity. Vinglycinate a glycinate

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called also the multidrug transporter. This protein is a product of multidrug resistance gene MDR1 and a member of family of ATP-dependent transporters (

1793: 3370: 335:, the microtubules required for cell division begins to form and grow towards the newly formed chromosomes forming a bundle of microtubules called the 308: 1714:

is a natural metabolite of the mammalian hormone oestradiol and is formed by oxidation in the liver. 2-methoxyestradiol is cytotoxic to several

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of Rome in 55 A.D. Dolastatins 10 and 15 are novel pentapeptides and exhibit powerful antimitotic properties. They are cytotoxic in a number of

6401: 5685: 5629: 5319: 3636: 2234: 1766:, inhibited cell mitosis and induced formation of stable tubulin polymer in vitro and considered to be more effective than paclitaxel with EC 2186: 2212: 2710:

Abal, M.; Andreu, J.; Barasoain, I. (2003). "Taxanes: Microtubule and Centrosome Targets, and Cell Cycle Dependent Mechanisms of Action".

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Chen, Jing; Liu, Tao; Dong, Xiaowu; Hu, Yongzhou (2009). "Recent Development and SAR Analysis of Colchicine Binding Site Inhibitors".

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alkaloid resistant solid tumors. Results from animals studies indicated activity against colorectal, breast and lung cancer tissues.

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Pellegrini, Federico; Budman, Daniel R (2005). "Review: Tubulin Function, Action of Antitubulin Drugs, and New Drug Development".

1684:. The hemiasterlins are a family of potent cytotoxic peptides. Hemiasterlin A and hemiasterlin B show potent activity against the 3629: 1811:– flushing, localized skin reactions, rash (with or without) pruritus, chest tightness, back pain, dyspnea, drug fever, or chills 1564:

plant, is used to treat viral skin infections and synthetic analogues of the molecule are used to treat certain types of cancer.

1476:, advanced testicular cancer and advanced breast cancer. Vincristine is mainly used to treat acute leukemia and other lymphomas. 704: 680:

a) Colchicine binding site, includes the colchicine, combrestatin, 2-methoxyestradiol, methoxy benzenesulfonamides (E7010) etc.

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Fang, W.-; Liang, X.- (2005). "Recent Progress in Structure Activity Relationship and Mechanistic Studies of Taxol Analogues".

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at position 1 showed reduced activity. Preparation of 10-α-spiro epoxide and its 7-MOM ether gave compounds having comparable

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and undergoes several growing and shortening periods in tuning with the back and forth oscillations of the chromosomes. In

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Discover new compounds active against drug-resistant cancers with different mechanism than drugs have been already known.

96:). Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in 4626: 4222: 1935:, but it has not been used for cancer treatment. First anticancer drugs approved for clinical use were Vinca alkaloids, 1487: 913: 1902:

limit – higher doses cause high toxicity and long-term use lead to cumulative neurotoxicity and hematopoietic toxicity.

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and tubulin assembly activity as that of paclitaxel. Substitution with C-6-α-OH and C-6-β-OH gave analogues which were

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derived from the C-17-OH group of vinblastine showed similar antitumor activity and toxicity as that of vinblastine.

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Attard, Gerhardt; Greystoke, Alastair; Kaye, Stan; De Bono, Johann (2006). "Update on tubulin-binding agents".

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Islam, Mohd.; Iskander, Magdy (2004). "Microtubulin Binding Sites as Target for Developing Anticancer Agents".

1701: 1628: 496: 320: 100:(the study of chromosomes), where they stop cell division at a stage where chromosomes can be easily examined. 17: 3378: 1910: 550:

dimer is inactive. Structural variation at C-15'- C-20' in the velbanamine ring is well tolerated. The upper

6406: 6336: 5634: 5324: 5231: 5049: 4764: 4250: 4098: 4025: 3547:(1999). "Clinical pharmacology of anticancer agents in relation to formulations and administration routes". 543: 416: 211:

during various stages of mitosis. Therefore, microtubule dynamics is an important target for the developing

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Lyseng-Williamson, K. A.; Fenton, C. (2005). "Docetaxel: A Review of its Use in Metastatic Breast Cancer".

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give a pipe-like structure called the microtubule. The head to tail arrangement of the hetero dimers gives

6373: 6020: 5129: 5119: 4852: 4694: 1970:, in 1967 by Monroe Wall and Mansukh Wani but, its tubulin inhibition activity was not known until 1979. 1349:, so through the inactivation of the microtubule function of a cell, taxanes inhibit the cell's division. 470: 253: 186: 3395: 3139: 2327:

Jordan, M. (2012). "Mechanism of Action of Antitumor Drugs that Interact with Microtubules and Tubulin".

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Table: Tubulin inhibitors with their binding sites, therapeutic uses and stages of clinical development.

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treatment for ovarian, breast, lung, and colon cancer and the second line treatment for AIDS-related

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has achieved great success as an anti-cancer drug, yet there has been continuous effort to improve its

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into microtubule polymers. This interrupts cell division, usually during the mitosis (M) phase of the

5671: 4799: 4676: 4197: 4113: 1864: 1855: 1749: 1416: 1113: 761: 273: 1596: 1172: 840: 6163: 5979: 5084: 4984: 4963: 4684: 4506: 4338: 4069: 3965: 1948: 1931: 1899: 1738: 1537: 1464: 1420: 1369: 1341:, they are now synthesized artificially. Their principal mechanism is the disruption of the cell's 1153: 1148: 977: 382: 376: 277: 2238: 883: 6326: 6296: 6291: 4142: 3607: 3328: 3255: 2830: 2561: 2502: 2448: 2133: 1711: 1231: 937: 5291: 2781:

Lixin Zhang, Arnold L. Demain (2005), Natural products: drug discovery and therapeutic medicine.

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The first known compound which binds to tubulin was colchicine, it was isolated from the autumn

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Tubulin inhibitors thus act by interfering with the dynamics of the microtubule, i.e., growing (

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TitoFojo, The role of microtubules in Cell Biology, Neurobiology and Oncology, Humana Press.

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In clinical use; 207 Phase I–III trials in the United States; TL00139 is in Phase I trials

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tubulin dimers whereas paclitaxel binding sites are located only in assembled tubulin. The

5913: 5903: 5492: 4710: 4672: 4463: 3885: 3800: 3399: 2789: 2477:

Jordan, Mary Ann; Wilson, Leslie (2004). "Microtubules as a target for anticancer drugs".

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of GTP permits the disassembly and the regulation of the microtubule system; however, the

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Kuppens, Isa (2006). "Current State of the Art of New Tubulin Inhibitors in the Clinic".

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Please help update this article to reflect recent events or newly available information.

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is an mitotic inhibitor that is used as an antifungal drug. It inhibits the assembly of

6412: 6343: 6286: 6256: 6241: 6009: 5898: 5640: 5428: 5418: 5330: 4864: 4455: 3949: 3813: 3700: 3670: 3657: 3207: 3182: 2886: 2861: 2153: 2118: 1860: 1757: 1634: 1428: 1361: 1300: 1210: 1118: 1018: 924: 875: 803: 618: 547: 540: 527: 364: 200: 3003: 6439: 6246: 6142: 6116: 5923: 5875: 5841: 5796: 5766: 5605: 5423: 5204: 5164: 4534: 4407: 4288: 4231: 3989: 3938: 3085: 3050: 1826: 1365: 828: 509: 204: 3611: 2565: 2506: 2452: 1183: 174:

are mitotic inhibitors used in the treatment of gout and nail fungus, respectively.

6368: 6353: 6266: 6196: 6112: 5946: 5941: 5933: 5928: 5918: 5908: 5826: 5816: 5811: 5801: 5786: 5776: 5761: 5702: 5698: 5546: 5449: 5389: 5251: 5215: 5099: 5089: 5043: 5039: 5001: 4909: 4699: 4638: 4634: 4615: 4610: 4589: 4578: 4392: 4386: 4372: 4367: 4298: 4293: 4246: 4132: 3999: 3979: 3908: 3857: 3847: 3661: 3653: 3332: 3259: 2113: 2083: 1997: 1623: 1610: 1585: 1572: 853: 639: 634: 556: 513: 504: 466: 340: 281: 196: 171: 97: 73: 3183:"An overview of tubulin inhibitors that interact with the colchicine binding site" 2834: 2649: 2632: 2289: 2272: 1223: 347:

this spindle attaches itself to the chromosomes at a particular point called the

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Examples of mitotic inhibitors frequently used in the treatment of cancer include

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Lakhani, Nehal J.; Sarkar, Mohamadi A.; Venitz, Jurgen; Figg, William D. (2003).

288:') and the frequency of transition from shortening to growth or pause (called a ' 6387: 6348: 6306: 6276: 6177: 6121: 6057: 6045: 5893: 5885: 5880: 5851: 5846: 5836: 5831: 5806: 5781: 5614: 5609: 5535: 5500: 5459: 5454: 5296: 5276: 5261: 5256: 5241: 5199: 5169: 5109: 5079: 5023: 4996: 4869: 4810: 4782: 4772: 4725: 4689: 4605: 4567: 4549: 4544: 4524: 4501: 4472: 4450: 4430: 4420: 4271: 4256: 4236: 4122: 4053: 4039: 3994: 3927: 3922: 3899: 3874: 3842: 3785: 3748: 3725: 3710: 3705: 3690: 3544: 3316: 3140:"The Effects of Vinflunine, Vinorelbine, and Vinblastine on Centromere Dynamics" 2208: 2148: 2103: 2098: 2093: 2088: 2073: 1940: 1936: 1873: 1868: 1577: 1503: 1479: 1469: 1459: 1455: 1435: 1425: 1379: 1357: 1342: 1338: 1078: 1073: 1068: 797: 791: 772: 756: 397: 348: 285: 228: 208: 192: 163: 159: 155: 85: 69: 3478: 3072:

Clarke, S. J.; Rivory, L. P. (1999). "Clinical Pharmacokinetics of Docetaxel".

2964: 2688: 1956:) plant at the University of Western Ontario in 1958. First drug belong to the 1867:). P-glycoprotein occurs in every organism and serves to protect the body from 1282: 1256: 375:

analogues. These three classes of drugs seems to operate by slightly different

6377: 6358: 6321: 6316: 6301: 6271: 6251: 6216: 6136: 6131: 6126: 6087: 6066: 6031: 5984: 5821: 5771: 5756: 5720: 5694: 5584: 5568: 5526: 5510: 5505: 5444: 5413: 5398: 5286: 5189: 5184: 5159: 5154: 5144: 5139: 5134: 5104: 5094: 5059: 5054: 5034: 4989: 4977: 4952: 4947: 4937: 4919: 4914: 4904: 4899: 4857: 4845: 4833: 4805: 4792: 4787: 4757: 4720: 4715: 4653: 4648: 4594: 4539: 4491: 4477: 4425: 4412: 4381: 4314: 4303: 4276: 4266: 4261: 4207: 4162: 4157: 4058: 4022: 3954: 3944: 3933: 3917: 3869: 3852: 3828: 3780: 3768: 3720: 3595: 3243: 3198: 3138:

Okouneva, Tatiana; Hill, Bridget T.; Wilson, Leslie; Jordan, Mary Ann (2003).

2143: 2123: 2108: 1961: 1744: 1727: 1679: 1528: 1523: 1509: 1353: 1274: 1269: 1205: 1108: 1093: 1005: 967: 905: 899: 815: 643: 517: 434: 429: 425: 412: 408: 372: 328: 167: 147: 128: 93: 77: 37: 2760: 2725: 2394: 2340: 1345:

function by stabilizing microtubule formation. Microtubules are essential to

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nausea, vomiting, diarrhea, constipation, paralytic ileus, urinary retention

1721: 1670: 1561: 1493: 1439: 1375: 1289: 1264: 1190: 1164: 1140: 1100: 988: 781: 568: 357: 344: 151: 104: 3603: 3568: 3560: 3526: 3486: 3439: 3324: 3251: 3216: 3155: 3093: 3058: 2972: 2930: 2895: 2768: 2733: 2696: 2658: 2606: 2597: 2580: 2498: 2444: 2402: 2348: 2298: 524:

ring is found to play an important role during interaction with tubulin.

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Terwogt, Jetske M.Meerum; Schellens, Jan H.M.; Huinink, Wim W.ten Bokkel;

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co-administration of P-gp and cytochrome inhibitors with anticancer drugs.

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concentration in the target, below therapeutic level. Efflux is caused by

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exhibit primarily dynamic instability, treadmilling or a mixture of both.

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Elucidation of all resistance mechanisms and design drugs which avoid it.

1653: 1532: 1497: 1483: 994: 777: 648: 551: 488: 457: 352: 332: 136: 112: 108: 3230:

Molad, Yair (2002). "Update on colchicine and its mechanism of action".

2819:

10.1002/(SICI)1098-1128(199603)16:2<207::AID-MED4>3.0.CO;2-4

2550:

10.1002/(SICI)1098-1128(199807)18:4<259::AID-MED3>3.0.CO;2-U

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Gordaliza, M. (2008). "Natural products as leads to anticancer drugs".

2068: 1957: 1662: 1346: 1328: 1324: 1319: 1086: 973: 820: 622: 560: 521: 461: 269: 249:(MTOCs), which are a network of microtubule associated proteins (MAP). 132: 124: 120: 116: 89: 57: 2922: 2877: 1242: 672:, includes the paclitaxel, epothilone, docetaxel, discodermolide etc. 227:

subunits, α- and β-tubulin. These two subunits combine to form an α,β-

3743: 2078: 1926: 1618: 1582: 289: 123:). Mitotic inhibitors interfere with the assembly and disassembly of 103:

Mitotic inhibitors are derived from natural substances such as plant

3415: 3300: 2987: 2802: 2490: 1665:, and thought to be the source of poison used to murder the son of 5731: 2803:"Antimitotic natural products and their interactions with tubulin" 1614: 1412: 1390: 1333: 526: 475: 444: 420: 381: 303: 181: 31: 5385: 1685: 1542: 1249: 909: 65: 32: 5667: 5357: 3625: 2988:"Treatment of HIV-associated Kaposi's sarcoma with paclitaxel" 2862:"Tubulin-Interactive Natural Products as Anticancer Agents(1)" 2020: 919:

Approved in 2009 by FDA under the Unapproved Drugs Initiative

3357: 491:

and develop analogues which are more active and have greater

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is typically isolated from the leaves of the Brazilian tree

559:

at C-19' position of vinorelbine dramatically increased the

276:

polymers and exhibit two kinds of dynamic behaviors : '

2472: 2470: 2468: 2466: 2464: 2462: 1885:

Marginal clinical efficacy – often compounds show activity

80:

apart when a cell divides. Mitotic inhibitors are used in

2783:

Natural products: drug discovery and therapeutic medicine

2177: 2175: 1964:, discovered in extracts from the bark of the yew tree, 1799:

stomatitis (ulceration of the lips, tongue, oral cavity)

3409: 3407: 3181:

Lu Y, Chen J, Xiao M, Li W, Miller DD (November 2012).

2633:"Microtubule Active Agents: Beyond the Taxane Frontier" 1622:

sp. GSV 224. The cryptophycins are a family of related

411:

enhances microtubule polymerization promoting both the

2581:"Microtubule-targeted anticancer agents and apoptosis" 2946: 2944: 2942: 2940: 2418: 2416: 2414: 2412: 2183:"What Are the Different Types of Chemotherapy Drugs?" 520:

to paclitaxel in tubulin assembly assay. Finally the

1677:

Hemiasterlins were isolated from the marine sponge,

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In clinical use; 108 combination trials in progress

567:

studies involve the vindoline portion of bis-indole

6229: 6205: 6186: 6162: 6155: 6100: 6079: 6056: 6030: 6019: 5978: 5955: 5865: 5746: 5730: 5719: 5710: 5577: 5559: 5519: 5491: 5482: 5437: 5406: 5397: 5011: 4962: 4742: 4735: 4671: 4625: 4558: 4515: 4352: 4337: 4217: 4187: 4112: 4097: 4068: 3964: 3884: 3827: 3810: 3799: 3735: 3688: 3669: 1814:

musculoskeletal effects – arthralgia and/or myalgia

1730:was isolated from the bark of the Pacific yew tree 767:in clinical use; 22 combination trials in progress 327:Microtubule is involved in different stages of the 207:by involving in the movement and attachment of the 3301:"2-Methoxyestradiol, a Promising Anticancer Agent" 3275:"Fighting Cancer with a Pinch of Parsley and Dill" 1424:(Madagascar Periwinkle). Vinca alkaloids inhibit 3279:GEN – Genetic Engineering and Biotechnology News 1446:, non-small cell lung cancer, breast cancer and 3107: 3105: 3103: 2329:Current Medicinal Chemistry. Anti-Cancer Agents 1946:They were isolated from extracts leaves of the 407:In contrast to colchicine and vinca alkaloids, 18:Discovery and development of tubulin inhibitors 1450:. It is also a component in a large number of 5679: 5369: 3637: 1889:but do not have antitumor activity in clinic. 1747:are derived from a fermenting soil bacteria, 1462:were isolated from the Madagascar periwinkle 1000:8 trials in the United States (Phases I–III) 8: 3371:"Chemotherapy-induced Peripheral Neuropathy" 2670: 2668: 2322: 2320: 2318: 2316: 2314: 2312: 2310: 2308: 3500: 3498: 3496: 1694:is isolated from the South African Willow, 6159: 6027: 5743: 5727: 5716: 5686: 5672: 5664: 5488: 5403: 5376: 5362: 5354: 4739: 4349: 4109: 3824: 3807: 3685: 3644: 3630: 3622: 2626: 2624: 2622: 2620: 2618: 2616: 1794:chemotherapy-induced peripheral neuropathy 1288: 1281: 1255: 1248: 1241: 1222: 1196: 1189: 1182: 1163: 1139: 1132: 1125: 1092: 1085: 1059: 1052: 1045: 687:Binding site of different drugs on tubulin 469:ring systems to ring B resulted in highly 203:and mitosis. They play a critical role in 3538: 3536: 3206: 2885: 2648: 2596: 2288: 2185:. American Cancer Society. Archived from 92:that eventually spread through the body ( 2531: 2529: 2527: 2525: 1031: 726: 2266: 2264: 2262: 2260: 2258: 2256: 2235:"Treatment Options: Mitotic Inhibitors" 2171: 1641:, and later from the unrelated sponges 685: 3416:"Mechanisms of cancer drug resistance" 3391:Hazardous Substances Data Bank (HSDB) 2631:Morris, P. G.; Fornier, M. N. (2008). 2376: 2374: 2372: 2370: 2368: 2366: 2364: 2362: 2360: 2358: 664:I. Tubulin depolymerization inhibitors 810:in progress (single and combination) 676:II. Tubulin polymerization inhibitors 441:Structure activity relationship (SAR) 76:, which are structures that pull the 7: 3432:10.1146/annurev.med.53.082901.103929 1613:52 was isolated from the blue–green 1496:—used to treat leukaemia, lymphoma, 1378:—used to treat breast, ovarian, and 1337:(yews). Originally derived from the 1331:produced by the plants of the genus 980:; trials with numerous other tumours 3913:ribonucleotide reductase inhibitors 3584:Clinical and Translational Oncology 3446:from the original on 13 August 2024 3162:from the original on 13 August 2024 2841:from the original on 22 August 2020 2749:Mini-Reviews in Medicinal Chemistry 2677:Mini-Reviews in Medicinal Chemistry 2383:Mini-Reviews in Medicinal Chemistry 2215:from the original on 13 August 2024 1652:Dolastatins were isolated from the 437:death in paclitaxel treated cells. 60:, or cell division, and is used in 4079:Ribonucleotide reductase inhibitor 4035:Ribonucleotide reductase inhibitor 3273:Writer, GEN Staff (29 June 2016). 1486:, breast cancer, lung cancer, and 929:Potential vascular-targeting agent 871:Potential vascular-targeting agent 40:, a widely used mitotic inhibitor. 25: 3838:Dihydrofolate reductase inhibitor 3339:from the original on 25 June 2023 3018:from the original on 26 June 2019 2209:"Definition of mitotic inhibitor" 1500:, breast cancer, and lung cancer. 400:during the metaphase of mitosis. 223:Microtubules are composed of two 3369:del Pino BM (23 February 2010). 3086:10.2165/00003088-199936020-00002 3051:10.2165/00003495-200565170-00007 2025: 1535:derived from the autumn crocus ( 1099: 715: 703: 691: 6169:thymidylate synthase inhibitors 1983:agents with better properties 386:Tubulin inhibitors binding site 3975:Thymidylate synthase inhibitor 3865:Thymidylate synthase inhibitor 3414:Gottesman, Michael M. (2002). 2860:Kingston, David G. I. (2009). 745:Stage of clinical development 247:Microtubule organizing centers 195:are the key components of the 1: 3895:Adenosine deaminase inhibitor 3736:Block microtubule disassembly 3144:Molecular Cancer Therapeutics 3004:10.1016/S0140-6736(95)92654-2 2953:Current Clinical Pharmacology 2650:10.1158/1078-0432.CCR-08-0169 2290:10.1158/1535-7163.MCT-09-0366 2277:Molecular Cancer Therapeutics 2237:. Drug Digest. Archived from 2211:. National Cancer Institute. 1909:Poor penetration through the 764:, testicular germ cell cancer 733:Classes of tubulin inhibitors 710:Vinblastine bound to tubulin. 415:and elongation phases of the 252:Two molecules of energy rich 3519:10.1016/j.patbio.2005.03.003 3232:Current Rheumatology Reports 1575:, derived from a species of 1488:acute lymphoblastic leukemia 1299: 1296: 1273: 1268: 1263: 1230: 1214: 1209: 1204: 1171: 1157: 1152: 1147: 1117: 1112: 1107: 1077: 1072: 1067: 1010:Paclitaxel-resistant tumours 914:familial mediterranean fever 722:Colchicine bound to tubulin. 531:SAR of Vinblastine analogues 331:. During the first stage or 5484:Xanthine oxidase inhibitors 3467:Current Cancer Drug Targets 3377:. p. 6. Archived from 3317:10.1592/phco.23.2.165.32088 2911:Journal of Natural Products 2866:Journal of Natural Products 2713:Current Cancer Drug Targets 976:, breast and lung tumours, 961:Depolymerization inhibitors 480:SAR of paclitaxel analogous 449:SAR of colchicine analogous 139:and the general use of the 56:, is a drug that inhibits 6467: 3479:10.2174/156800907783220499 3358:http://www.paclitaxel.org/ 2965:10.2174/157488406775268200 2807:Medicinal Research Reviews 2689:10.2174/138955709789055234 2538:Medicinal Research Reviews 1809:hypersensitivity reactions 1521: 1401: 1380:non-small cell lung cancer 1317: 825:non-small-cell lung cancer 796:Solid tumours, lymphomas, 749: 632: 231:which then assembles in a 6396: 6237:bromochlorosalicylanilide 6207:Aminoacyl tRNA synthetase 5624: 5314: 5195:Omacetaxine mepesuccinate 5075:Ciltacabtagene autoleucel 5065:Brexucabtagene autoleucel 3596:10.1007/s12094-007-0138-9 3420:Annual Review of Medicine 3393:http://toxnet.nlm.nih.gov 3244:10.1007/s11926-002-0073-2 3199:10.1007/s11095-012-0828-z 3074:Clinical Pharmacokinetics 2034:This section needs to be 1921:Discovery and development 1629:drug-resistant cell lines 1237: 1178: 1041: 1034: 963: 960: 895: 752: 750:Polymerization inhibitors 88:are able to grow through 5247:Talimogene laherparepvec 5180:Nadofaragene firadenovec 5150:Lisocabtagene maraleucel 4099:Topoisomerase inhibitors 4018:DNA polymerase inhibitor 3549:Cancer Treatment Reviews 2761:10.2174/1389557053402837 2726:10.2174/1568009033481967 2637:Clinical Cancer Research 2579:Bhalla, Kapil N (2003). 2395:10.2174/1389557043402946 2341:10.2174/1568011023354290 1702:multiple drug resistance 1637:was first isolated from 1368:, and advanced forms of 997:, brain and lung tumours 739:Related drugs or analogs 187:Formation of microtubule 5050:Axicabtagene ciloleucel 3654:chemotherapeutic agents 3113:"Vincristine (Oncovin)" 2788:30 October 2023 at the 1978:Future drug development 1805:bone marrow suppression 698:Taxol bound to tubulin. 670:Paclitaxel site ligands 417:polymerization reaction 111:made of smaller units ( 27:Cell division inhibitor 6021:Squalene monooxygenase 5858:Systemic: ketoconazole 5232:Sitimagene ceradenovec 5130:Idecabtagene vicleucel 4695:Methyl aminolevulinate 3561:10.1053/ctrv.1998.0107 2801:Hamel, Ernest (1996). 2598:10.1038/sj.onc.1207233 1399: 563:activity. Most of the 532: 481: 450: 387: 316: 254:guanosine triphosphate 189: 72:. These drugs disrupt 41: 6049:Systemic: terbinafine 4706:Porphyrin derivatives 4402:Melphalan flufenamide 4049:Hypomethylating agent 3658:antineoplastic agents 2479:Nature Reviews Cancer 2437:10.1081/CNV-200055970 2271:Perez, E. A. (2009). 1763:Discodermia dissoluta 1658:Dolabella auricularia 1452:chemotherapy regimens 1394: 655:Tubulin binding drugs 530: 479: 448: 393:conformational change 385: 315: 268:Microtubules are not 258:guanosine diphosphate 185: 50:microtubule inhibitor 35: 6337:Whitfield's ointment 6164:Pyrimidine analogues 5980:Polyene antimycotics 5035:Asparagine depleters 4964:Receptor antagonists 4878:+abiraterone acetate 3398:11 June 2019 at the 3381:on 11 December 2011. 2425:Cancer Investigation 1865:ATP-binding cassette 1856:Multidrug resistance 1750:Sorangium cellulosum 1417:hallucinogenic plant 1347:mitotic reproduction 802:In clinical use; 29 272:but they are highly 264:Microtubule dynamics 5085:Denileukin diftitox 4985:Retinoid X receptor 4685:Aminolevulinic acid 4507:Triethylenemelamine 4339:Crosslinking of DNA 4070:Deoxyribonucleotide 4009:+gimeracil/oteracil 3507:Pathologie Biologie 3375:NCI Cancer Bulletin 2241:on 16 February 2007 1949:Catharanthus roseus 1932:Colchicum autumnale 1911:blood–brain barrier 1874:endocytosis process 1639:Halichondria okadai 1602:Ateleia glazioviana 1538:Colchicum autumnale 1465:Catharanthus roseus 1421:Catharanthus roseus 848:Phase III finished 729: 629:Use in cytogenetics 300:Mechanism of action 278:dynamic instability 90:continuous division 6451:Mitotic inhibitors 6423:Never to phase III 6327:tribromometacresol 6297:sodium thiosulfate 6292:selenium disulfide 6188:Mitotic inhibitors 5651:Never to phase III 5561:Mitotic inhibitors 5341:Never to phase III 4143:Etirinotecan pegol 2134:2-Methoxyestradiol 1712:2-Methoxyestradiol 1474:Hodgkin's lymphoma 1444:Hodgkin's lymphoma 1400: 1232:2-Methoxyestradiol 1036:Tubulin inhibitors 938:2-Methoxyestradiol 727: 649:hypotonic solution 533: 482: 451: 388: 317: 190: 42: 6433: 6432: 6225: 6224: 6151: 6150: 6102:β-glucan synthase 6096: 6095: 6075: 6074: 5974: 5973: 5661: 5660: 5555: 5554: 5478: 5477: 5351: 5350: 5310: 5309: 5267:Tigilanol tiglate 4744:Enzyme inhibitors 4667: 4666: 4663: 4662: 4363:Nitrogen mustards 4333: 4332: 4093: 4092: 3795: 3794: 3045:(17): 2513–2531. 2923:10.1021/np030420c 2878:10.1021/np800568j 2055: 2054: 1647:Phankella carteri 1560:derived from the 1448:testicular cancer 1306: 1305: 1179:Colchicine domain 1030: 1029: 896:Colchicine domain 762:Hodgkin's disease 313: 213:anti-cancer drugs 115:) of the protein 54:tubulin inhibitor 46:mitotic inhibitor 36:The structure of 16:(Redirected from 6458: 6332:undecylenic acid 6282:potassium iodide 6160: 6028: 5744: 5728: 5717: 5688: 5681: 5674: 5665: 5493:purine analogues 5489: 5404: 5378: 5371: 5364: 5355: 5272:Tisagenlecleucel 5029:Arsenic trioxide 4740: 4673:Photosensitizers 4464:Alkyl sulfonates 4378:Cyclophosphamide 4350: 4289:Anthracenediones 4110: 4084:Hydroxycarbamide 3825: 3808: 3686: 3646: 3639: 3632: 3623: 3616: 3615: 3579: 3573: 3572: 3540: 3531: 3530: 3502: 3491: 3490: 3462: 3456: 3455: 3453: 3451: 3411: 3402: 3389: 3383: 3382: 3366: 3360: 3355: 3349: 3348: 3346: 3344: 3296: 3290: 3289: 3287: 3285: 3270: 3264: 3263: 3227: 3221: 3220: 3210: 3178: 3172: 3171: 3169: 3167: 3135: 3129: 3128: 3126: 3124: 3115:. Archived from 3109: 3098: 3097: 3069: 3063: 3062: 3034: 3028: 3027: 3025: 3023: 2983: 2977: 2976: 2948: 2935: 2934: 2906: 2900: 2899: 2889: 2857: 2851: 2850: 2848: 2846: 2798: 2792: 2779: 2773: 2772: 2744: 2738: 2737: 2707: 2701: 2700: 2672: 2663: 2662: 2652: 2628: 2611: 2610: 2600: 2576: 2570: 2569: 2533: 2520: 2517: 2511: 2510: 2474: 2457: 2456: 2420: 2407: 2406: 2389:(10): 1077–104. 2378: 2353: 2352: 2324: 2303: 2302: 2292: 2268: 2251: 2250: 2248: 2246: 2231: 2225: 2224: 2222: 2220: 2205: 2199: 2198: 2196: 2194: 2179: 2050: 2047: 2041: 2029: 2028: 2021: 1967:Taxus brevifolia 1777: 1773: 1739:Kaposi's sarcoma 1733:Taxus brevifolia 1716:tumor cell lines 1667:Emperor Claudius 1643:Axinella carteri 1415:produced by the 1396:Skeletal formula 1370:Kaposi's sarcoma 1339:Pacific yew tree 1292: 1285: 1259: 1252: 1245: 1226: 1200: 1193: 1186: 1167: 1143: 1136: 1129: 1103: 1096: 1089: 1063: 1056: 1049: 1032: 978:Kaposi's sarcoma 742:Therapeutic uses 730: 719: 707: 695: 647:and placed in a 604:and I-Vla(P)-(OC 314: 225:globular protein 82:cancer treatment 21: 6466: 6465: 6461: 6460: 6459: 6457: 6456: 6455: 6436: 6435: 6434: 6429: 6428: 6413:Clinical trials 6392: 6221: 6201: 6182: 6167: 6147: 6104: 6092: 6071: 6052: 6048: 6023: 6015: 6007: 5982: 5970: 5951: 5904:fosravuconazole 5861: 5737: 5736:lanosterol 14α- 5723: 5712: 5706: 5692: 5662: 5657: 5656: 5641:Clinical trials 5620: 5573: 5551: 5515: 5474: 5433: 5393: 5384:Drugs used for 5382: 5352: 5347: 5346: 5331:Clinical trials 5306: 5012:Other/ungrouped 5007: 4958: 4731: 4711:Porfimer sodium 4659: 4621: 4554: 4511: 4341: 4329: 4213: 4183: 4101: 4089: 4064: 3960: 3880: 3816: 3814:antimetabolites 3812: 3811:DNA precursors/ 3803: 3801:DNA replication 3791: 3731: 3701:Vinca alkaloids 3677: 3665: 3650: 3620: 3619: 3581: 3580: 3576: 3545:Beijnen, Jos H. 3542: 3541: 3534: 3504: 3503: 3494: 3464: 3463: 3459: 3449: 3447: 3413: 3412: 3405: 3400:Wayback Machine 3390: 3386: 3368: 3367: 3363: 3356: 3352: 3342: 3340: 3305:Pharmacotherapy 3298: 3297: 3293: 3283: 3281: 3272: 3271: 3267: 3229: 3228: 3224: 3193:(11): 2943–71. 3180: 3179: 3175: 3165: 3163: 3137: 3136: 3132: 3122: 3120: 3119:on 29 June 2007 3111: 3110: 3101: 3071: 3070: 3066: 3036: 3035: 3031: 3021: 3019: 2998:(8966): 26–28. 2985: 2984: 2980: 2950: 2949: 2938: 2908: 2907: 2903: 2859: 2858: 2854: 2844: 2842: 2800: 2799: 2795: 2790:Wayback Machine 2780: 2776: 2746: 2745: 2741: 2709: 2708: 2704: 2683:(10): 1174–90. 2674: 2673: 2666: 2643:(22): 7167–72. 2630: 2629: 2614: 2591:(56): 9075–86. 2578: 2577: 2573: 2535: 2534: 2523: 2518: 2514: 2491:10.1038/nrc1317 2476: 2475: 2460: 2422: 2421: 2410: 2380: 2379: 2356: 2326: 2325: 2306: 2270: 2269: 2254: 2244: 2242: 2233: 2232: 2228: 2218: 2216: 2207: 2206: 2202: 2192: 2190: 2189:on 17 July 2007 2181: 2180: 2173: 2168: 2161:, a newer agent 2129:Combretastatins 2064:Medicinal molds 2060: 2051: 2045: 2042: 2039: 2030: 2026: 1980: 1943:in the 1960s. 1923: 1917: 1896:Bioavailability 1882: 1853: 1851:Drug resistance 1844:bioavailability 1840:cytochrome P450 1835: 1817:severe weakness 1790: 1785: 1775: 1771: 1769: 1697:Combretum afrum 1692:Combretastatins 1593: 1570: 1558:Podophyllotoxin 1555: 1553:Podophyllotoxin 1526: 1520: 1482:—used to treat 1438:—used to treat 1409:Vinca alkaloids 1406: 1404:Vinca alkaloids 1389: 1387:Vinca alkaloids 1356:—used to treat 1322: 1316: 1311: 1309:Specific agents 1158:Hemiasterlin A 1114:Cryptophycin 52 1037: 925:Combretastatins 808:clinical trials 723: 720: 711: 708: 699: 696: 678: 666: 657: 642:, the study of 637: 631: 615: 611: 607: 603: 599: 595: 591: 587: 583: 579: 575: 502: 493:bioavailability 443: 369:vinca alkaloids 337:mitotic spindle 304: 302: 266: 221: 180: 141:vinca alkaloids 62:treating cancer 28: 23: 22: 15: 12: 11: 5: 6464: 6462: 6454: 6453: 6448: 6438: 6437: 6431: 6430: 6427: 6426: 6425: 6424: 6421: 6410: 6404: 6398: 6397: 6394: 6393: 6391: 6390: 6385: 6380: 6371: 6366: 6361: 6356: 6351: 6346: 6344:citronella oil 6340: 6339: 6334: 6329: 6324: 6319: 6314: 6309: 6304: 6299: 6294: 6289: 6287:salicylic acid 6284: 6279: 6274: 6269: 6264: 6259: 6257:crystal violet 6254: 6249: 6244: 6242:chlorophetanol 6239: 6233: 6231: 6227: 6226: 6223: 6222: 6220: 6219: 6212: 6210: 6203: 6202: 6200: 6199: 6192: 6190: 6184: 6183: 6181: 6180: 6173: 6171: 6157: 6153: 6152: 6149: 6148: 6146: 6145: 6140: 6134: 6129: 6124: 6119: 6108: 6106: 6098: 6097: 6094: 6093: 6091: 6090: 6083: 6081: 6077: 6076: 6073: 6072: 6070: 6069: 6062: 6060: 6054: 6053: 6051: 6050: 6043: 6036: 6034: 6025: 6017: 6016: 6014: 6013: 6010:amphotericin B 6002: 5997: 5990: 5988: 5976: 5975: 5972: 5971: 5969: 5968: 5961: 5959: 5953: 5952: 5950: 5949: 5944: 5937: 5936: 5931: 5926: 5921: 5916: 5911: 5906: 5901: 5899:fosfluconazole 5896: 5889: 5888: 5883: 5878: 5871: 5869: 5863: 5862: 5860: 5859: 5855: 5854: 5849: 5844: 5839: 5834: 5829: 5824: 5819: 5814: 5809: 5804: 5799: 5794: 5789: 5784: 5779: 5774: 5769: 5764: 5759: 5752: 5750: 5741: 5725: 5714: 5708: 5707: 5693: 5691: 5690: 5683: 5676: 5668: 5659: 5658: 5655: 5654: 5653: 5652: 5649: 5638: 5632: 5626: 5625: 5622: 5621: 5619: 5618: 5612: 5603: 5598: 5587: 5581: 5579: 5575: 5574: 5572: 5571: 5565: 5563: 5557: 5556: 5553: 5552: 5550: 5549: 5544: 5538: 5529: 5523: 5521: 5517: 5516: 5514: 5513: 5508: 5503: 5497: 5495: 5486: 5480: 5479: 5476: 5475: 5473: 5472: 5467: 5462: 5457: 5452: 5447: 5441: 5439: 5435: 5434: 5432: 5431: 5429:Isobromindione 5426: 5421: 5419:Sulfinpyrazone 5416: 5410: 5408: 5401: 5395: 5394: 5383: 5381: 5380: 5373: 5366: 5358: 5349: 5348: 5345: 5344: 5343: 5342: 5339: 5328: 5322: 5316: 5315: 5312: 5311: 5308: 5307: 5305: 5304: 5299: 5294: 5289: 5284: 5279: 5274: 5269: 5264: 5259: 5254: 5249: 5244: 5239: 5234: 5229: 5224: 5218: 5207: 5202: 5197: 5192: 5187: 5182: 5177: 5172: 5167: 5162: 5157: 5152: 5147: 5142: 5137: 5132: 5127: 5122: 5117: 5112: 5107: 5102: 5097: 5092: 5087: 5082: 5077: 5072: 5067: 5062: 5057: 5052: 5047: 5031: 5026: 5021: 5015: 5013: 5009: 5008: 5006: 5005: 4993: 4981: 4968: 4966: 4960: 4959: 4957: 4956: 4950: 4945: 4940: 4935: 4923: 4917: 4912: 4907: 4902: 4891: 4885: 4880: 4872: 4865:PARP inhibitor 4861: 4849: 4837: 4825: 4824: 4823: 4818: 4813: 4808: 4796: 4790: 4785: 4780: 4775: 4761: 4748: 4746: 4737: 4733: 4732: 4730: 4729: 4723: 4718: 4713: 4702: 4697: 4692: 4687: 4681: 4679: 4669: 4668: 4665: 4664: 4661: 4660: 4658: 4657: 4651: 4646: 4641: 4631: 4629: 4623: 4622: 4620: 4619: 4613: 4608: 4597: 4592: 4587: 4582: 4570: 4564: 4562: 4556: 4555: 4553: 4552: 4547: 4542: 4537: 4532: 4527: 4521: 4519: 4517:Platinum-based 4513: 4512: 4510: 4509: 4504: 4499: 4494: 4482: 4481: 4475: 4459: 4458: 4453: 4448: 4443: 4433: 4428: 4416: 4415: 4410: 4405: 4395: 4390: 4384: 4375: 4370: 4358: 4356: 4347: 4335: 4334: 4331: 4330: 4328: 4327: 4322: 4317: 4312: 4307: 4301: 4296: 4285: 4279: 4274: 4269: 4264: 4259: 4254: 4244: 4239: 4232:Anthracyclines 4227: 4225: 4215: 4214: 4212: 4211: 4205: 4193: 4191: 4185: 4184: 4182: 4181: 4175: 4170: 4165: 4160: 4155: 4150: 4145: 4140: 4135: 4130: 4118: 4116: 4107: 4095: 4094: 4091: 4090: 4088: 4087: 4074: 4072: 4066: 4065: 4063: 4062: 4056: 4044: 4043: 4030: 4029: 4013: 4012: 4002: 3997: 3992: 3987: 3982: 3970: 3968: 3962: 3961: 3959: 3958: 3952: 3950:Mercaptopurine 3941: 3936: 3931: 3925: 3920: 3904: 3903: 3890: 3888: 3882: 3881: 3879: 3878: 3872: 3861: 3855: 3850: 3845: 3833: 3831: 3822: 3805: 3797: 3796: 3793: 3792: 3790: 3789: 3777: 3771: 3766: 3761: 3756: 3751: 3739: 3737: 3733: 3732: 3730: 3729: 3723: 3718: 3713: 3708: 3696: 3694: 3683: 3667: 3666: 3652:Intracellular 3651: 3649: 3648: 3641: 3634: 3626: 3618: 3617: 3590:(12): 767–76. 3574: 3532: 3492: 3457: 3403: 3384: 3361: 3350: 3291: 3265: 3222: 3173: 3130: 3099: 3064: 3029: 2978: 2936: 2901: 2852: 2793: 2774: 2739: 2720:(3): 193–203. 2702: 2664: 2612: 2571: 2521: 2512: 2458: 2408: 2354: 2304: 2283:(8): 2086–95. 2252: 2226: 2200: 2170: 2169: 2167: 2164: 2163: 2162: 2156: 2154:Discodermolide 2151: 2146: 2141: 2136: 2131: 2126: 2121: 2119:Halichondrin B 2116: 2111: 2106: 2101: 2096: 2091: 2086: 2081: 2076: 2071: 2066: 2059: 2056: 2053: 2052: 2033: 2031: 2024: 2019: 2018: 2015: 2012: 2005: 2001: 1993: 1989: 1979: 1976: 1922: 1919: 1915: 1914: 1907: 1903: 1897: 1894: 1890: 1881: 1878: 1861:P-glycoprotein 1852: 1849: 1834: 1831: 1830: 1829: 1824: 1821: 1818: 1815: 1812: 1806: 1803: 1800: 1797: 1789: 1786: 1784: 1781: 1780: 1779: 1767: 1758:Discodermolide 1755: 1742: 1725: 1719: 1709: 1705: 1689: 1675: 1661:, a small sea 1650: 1635:Halichondrin B 1632: 1607: 1606: 1597:Glaziovianin A 1592: 1589: 1569: 1566: 1554: 1551: 1522:Main article: 1519: 1516: 1515: 1514: 1507: 1501: 1491: 1477: 1429:polymerization 1402:Main article: 1398:of vinblastine 1388: 1385: 1384: 1383: 1373: 1362:ovarian cancer 1318:Main article: 1315: 1312: 1310: 1307: 1304: 1303: 1301:Discodermolide 1298: 1294: 1293: 1286: 1278: 1277: 1272: 1267: 1261: 1260: 1253: 1246: 1239: 1235: 1234: 1228: 1227: 1219: 1218: 1213: 1211:Combretastatin 1208: 1202: 1201: 1194: 1187: 1180: 1176: 1175: 1173:Hemiasterlin B 1169: 1168: 1160: 1159: 1156: 1151: 1145: 1144: 1137: 1130: 1122: 1121: 1119:Halichondrin B 1116: 1111: 1105: 1104: 1097: 1090: 1082: 1081: 1076: 1071: 1065: 1064: 1057: 1050: 1043: 1039: 1038: 1035: 1028: 1027: 1024: 1021: 1019:Discodermolide 1015: 1014: 1011: 1008: 1002: 1001: 998: 992: 985: 984: 981: 971: 965: 962: 958: 957: 954: 951: 947: 946: 943: 940: 934: 933: 930: 927: 921: 920: 917: 902: 897: 893: 892: 889: 886: 880: 879: 872: 869: 863: 862: 859: 856: 850: 849: 846: 843: 841:Crytophycin 52 837: 836: 831: 818: 812: 811: 800: 794: 788: 787: 784: 775: 769: 768: 765: 759: 754: 751: 747: 746: 743: 740: 737: 736:Binding domain 734: 725: 724: 721: 714: 712: 709: 702: 700: 697: 690: 688: 677: 674: 665: 662: 656: 653: 633:Main article: 630: 627: 619:semi-synthetic 613: 609: 605: 601: 597: 593: 592:, L-Ala(P)-(OC 589: 585: 581: 580:, d-Ala(P)-(OC 577: 573: 548:decarboxylated 544:configurations 541:stereochemical 500: 442: 439: 365:polymerization 301: 298: 265: 262: 220: 217: 201:cell signaling 179: 176: 135:into clinical 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 6463: 6452: 6449: 6447: 6444: 6443: 6441: 6422: 6420: 6417: 6416: 6414: 6411: 6408: 6405: 6403: 6400: 6399: 6395: 6389: 6386: 6384: 6381: 6379: 6375: 6372: 6370: 6367: 6365: 6362: 6360: 6357: 6355: 6352: 6350: 6347: 6345: 6342: 6341: 6338: 6335: 6333: 6330: 6328: 6325: 6323: 6320: 6318: 6315: 6313: 6310: 6308: 6305: 6303: 6300: 6298: 6295: 6293: 6290: 6288: 6285: 6283: 6280: 6278: 6275: 6273: 6270: 6268: 6265: 6263: 6260: 6258: 6255: 6253: 6250: 6248: 6247:chlorphenesin 6245: 6243: 6240: 6238: 6235: 6234: 6232: 6228: 6218: 6214: 6213: 6211: 6208: 6204: 6198: 6194: 6193: 6191: 6189: 6185: 6179: 6175: 6174: 6172: 6170: 6165: 6161: 6158: 6156:Intracellular 6154: 6144: 6143:ibrexafungerp 6141: 6138: 6135: 6133: 6130: 6128: 6125: 6123: 6120: 6118: 6117:anidulafungin 6114: 6113:echinocandins 6110: 6109: 6107: 6103: 6099: 6089: 6085: 6084: 6082: 6078: 6068: 6064: 6063: 6061: 6059: 6055: 6047: 6044: 6042: 6038: 6037: 6035: 6033: 6029: 6026: 6022: 6018: 6011: 6006: 6003: 6001: 5998: 5996: 5992: 5991: 5989: 5986: 5981: 5977: 5967: 5963: 5962: 5960: 5958: 5954: 5948: 5945: 5943: 5939: 5938: 5935: 5932: 5930: 5927: 5925: 5924:oteseconazole 5922: 5920: 5917: 5915: 5914:isavuconazole 5912: 5910: 5907: 5905: 5902: 5900: 5897: 5895: 5891: 5890: 5887: 5884: 5882: 5879: 5877: 5876:efinaconazole 5873: 5872: 5870: 5868: 5864: 5857: 5856: 5853: 5850: 5848: 5845: 5843: 5842:sertaconazole 5840: 5838: 5835: 5833: 5830: 5828: 5825: 5823: 5820: 5818: 5815: 5813: 5810: 5808: 5805: 5803: 5800: 5798: 5797:fenticonazole 5795: 5793: 5790: 5788: 5785: 5783: 5780: 5778: 5775: 5773: 5770: 5768: 5767:chlormidazole 5765: 5763: 5760: 5758: 5754: 5753: 5751: 5749: 5745: 5742: 5739: 5733: 5729: 5726: 5722: 5718: 5715: 5709: 5704: 5700: 5696: 5689: 5684: 5682: 5677: 5675: 5670: 5669: 5666: 5650: 5648: 5645: 5644: 5642: 5639: 5636: 5633: 5631: 5628: 5627: 5623: 5616: 5613: 5611: 5607: 5606:Urate oxidase 5604: 5602: 5599: 5597: 5594: 5591: 5588: 5586: 5583: 5582: 5580: 5576: 5570: 5567: 5566: 5564: 5562: 5558: 5548: 5545: 5542: 5539: 5537: 5533: 5530: 5528: 5525: 5524: 5522: 5518: 5512: 5509: 5507: 5504: 5502: 5499: 5498: 5496: 5494: 5490: 5487: 5485: 5481: 5471: 5468: 5466: 5463: 5461: 5458: 5456: 5453: 5451: 5448: 5446: 5443: 5442: 5440: 5436: 5430: 5427: 5425: 5424:Benzbromarone 5422: 5420: 5417: 5415: 5412: 5411: 5409: 5405: 5402: 5400: 5396: 5391: 5387: 5379: 5374: 5372: 5367: 5365: 5360: 5359: 5356: 5340: 5338: 5335: 5334: 5332: 5329: 5326: 5323: 5321: 5318: 5317: 5313: 5303: 5300: 5298: 5295: 5293: 5290: 5288: 5285: 5283: 5280: 5278: 5275: 5273: 5270: 5268: 5265: 5263: 5260: 5258: 5255: 5253: 5250: 5248: 5245: 5243: 5240: 5238: 5235: 5233: 5230: 5228: 5225: 5222: 5219: 5217: 5213: 5212: 5208: 5206: 5205:Tabelecleucel 5203: 5201: 5198: 5196: 5193: 5191: 5188: 5186: 5183: 5181: 5178: 5176: 5173: 5171: 5168: 5166: 5165:Lurbinectedin 5163: 5161: 5158: 5156: 5153: 5151: 5148: 5146: 5143: 5141: 5138: 5136: 5133: 5131: 5128: 5126: 5123: 5121: 5118: 5116: 5113: 5111: 5108: 5106: 5103: 5101: 5098: 5096: 5093: 5091: 5088: 5086: 5083: 5081: 5078: 5076: 5073: 5071: 5068: 5066: 5063: 5061: 5058: 5056: 5053: 5051: 5048: 5045: 5041: 5037: 5036: 5032: 5030: 5027: 5025: 5022: 5020: 5017: 5016: 5014: 5010: 5003: 4999: 4998: 4994: 4991: 4987: 4986: 4982: 4979: 4975: 4974: 4970: 4969: 4967: 4965: 4961: 4954: 4951: 4949: 4946: 4944: 4941: 4939: 4936: 4934: 4930: 4928: 4924: 4921: 4918: 4916: 4913: 4911: 4908: 4906: 4903: 4901: 4897: 4896: 4892: 4889: 4886: 4884: 4881: 4879: 4876: 4873: 4871: 4867: 4866: 4862: 4859: 4855: 4854: 4850: 4847: 4843: 4842: 4838: 4835: 4831: 4830: 4826: 4822: 4819: 4817: 4814: 4812: 4809: 4807: 4804: 4803: 4802: 4801: 4797: 4794: 4791: 4789: 4786: 4784: 4781: 4779: 4776: 4774: 4770: 4769: 4766: 4762: 4759: 4755: 4754: 4750: 4749: 4747: 4745: 4741: 4738: 4734: 4727: 4724: 4722: 4719: 4717: 4714: 4712: 4708: 4707: 4703: 4701: 4698: 4696: 4693: 4691: 4688: 4686: 4683: 4682: 4680: 4678: 4674: 4670: 4655: 4652: 4650: 4647: 4645: 4642: 4640: 4636: 4633: 4632: 4630: 4628: 4627:Intercalation 4624: 4617: 4614: 4612: 4609: 4607: 4603: 4602: 4598: 4596: 4593: 4591: 4588: 4586: 4583: 4580: 4576: 4575: 4571: 4569: 4566: 4565: 4563: 4561: 4557: 4551: 4548: 4546: 4543: 4541: 4538: 4536: 4535:Dicycloplatin 4533: 4531: 4528: 4526: 4523: 4522: 4520: 4518: 4514: 4508: 4505: 4503: 4500: 4498: 4495: 4493: 4490: 4488: 4484: 4483: 4479: 4476: 4474: 4470: 4467: 4465: 4461: 4460: 4457: 4454: 4452: 4449: 4447: 4444: 4441: 4437: 4434: 4432: 4429: 4427: 4424: 4422: 4418: 4417: 4414: 4411: 4409: 4408:Prednimustine 4406: 4403: 4399: 4396: 4394: 4391: 4388: 4385: 4383: 4379: 4376: 4374: 4371: 4369: 4366: 4364: 4360: 4359: 4357: 4355: 4351: 4348: 4345: 4340: 4336: 4326: 4323: 4321: 4318: 4316: 4313: 4311: 4308: 4305: 4302: 4300: 4297: 4295: 4291: 4290: 4286: 4283: 4280: 4278: 4275: 4273: 4270: 4268: 4265: 4263: 4260: 4258: 4255: 4252: 4248: 4245: 4243: 4240: 4238: 4234: 4233: 4229: 4228: 4226: 4224: 4223:Intercalation 4220: 4216: 4209: 4206: 4204: 4200: 4199: 4195: 4194: 4192: 4190: 4186: 4179: 4176: 4174: 4171: 4169: 4166: 4164: 4161: 4159: 4156: 4154: 4151: 4149: 4146: 4144: 4141: 4139: 4136: 4134: 4131: 4129: 4125: 4124: 4120: 4119: 4117: 4115: 4111: 4108: 4105: 4100: 4096: 4085: 4081: 4080: 4076: 4075: 4073: 4071: 4067: 4060: 4057: 4055: 4051: 4050: 4046: 4045: 4041: 4037: 4036: 4032: 4031: 4027: 4026:+daunorubicin 4024: 4020: 4019: 4015: 4014: 4010: 4006: 4003: 4001: 3998: 3996: 3993: 3991: 3990:Doxifluridine 3988: 3986: 3983: 3981: 3977: 3976: 3972: 3971: 3969: 3967: 3963: 3956: 3953: 3951: 3947: 3946: 3942: 3940: 3939:Rabacfosadine 3937: 3935: 3932: 3929: 3926: 3924: 3921: 3919: 3915: 3914: 3910: 3906: 3905: 3901: 3897: 3896: 3892: 3891: 3889: 3887: 3883: 3876: 3873: 3871: 3867: 3866: 3862: 3859: 3856: 3854: 3851: 3849: 3846: 3844: 3840: 3839: 3835: 3834: 3832: 3830: 3826: 3823: 3820: 3815: 3809: 3806: 3802: 3798: 3787: 3783: 3782: 3778: 3775: 3772: 3770: 3767: 3765: 3762: 3760: 3757: 3755: 3752: 3750: 3746: 3745: 3741: 3740: 3738: 3734: 3727: 3724: 3722: 3719: 3717: 3714: 3712: 3709: 3707: 3703: 3702: 3698: 3697: 3695: 3692: 3687: 3684: 3681: 3676: 3672: 3668: 3663: 3659: 3655: 3647: 3642: 3640: 3635: 3633: 3628: 3627: 3624: 3613: 3609: 3605: 3601: 3597: 3593: 3589: 3585: 3578: 3575: 3570: 3566: 3562: 3558: 3555:(2): 83–101. 3554: 3550: 3546: 3539: 3537: 3533: 3528: 3524: 3520: 3516: 3512: 3508: 3501: 3499: 3497: 3493: 3488: 3484: 3480: 3476: 3473:(8): 766–84. 3472: 3468: 3461: 3458: 3445: 3441: 3437: 3433: 3429: 3425: 3421: 3417: 3410: 3408: 3404: 3401: 3397: 3394: 3388: 3385: 3380: 3376: 3372: 3365: 3362: 3359: 3354: 3351: 3338: 3334: 3330: 3326: 3322: 3318: 3314: 3311:(2): 165–72. 3310: 3306: 3302: 3295: 3292: 3280: 3276: 3269: 3266: 3261: 3257: 3253: 3249: 3245: 3241: 3237: 3233: 3226: 3223: 3218: 3214: 3209: 3204: 3200: 3196: 3192: 3188: 3184: 3177: 3174: 3161: 3157: 3153: 3150:(5): 427–36. 3149: 3145: 3141: 3134: 3131: 3118: 3114: 3108: 3106: 3104: 3100: 3095: 3091: 3087: 3083: 3080:(2): 99–114. 3079: 3075: 3068: 3065: 3060: 3056: 3052: 3048: 3044: 3040: 3033: 3030: 3017: 3013: 3009: 3005: 3001: 2997: 2993: 2989: 2982: 2979: 2974: 2970: 2966: 2962: 2958: 2954: 2947: 2945: 2943: 2941: 2937: 2932: 2928: 2924: 2920: 2917:(2): 232–44. 2916: 2912: 2905: 2902: 2897: 2893: 2888: 2883: 2879: 2875: 2872:(3): 507–15. 2871: 2867: 2863: 2856: 2853: 2840: 2836: 2832: 2828: 2824: 2820: 2816: 2813:(2): 207–31. 2812: 2808: 2804: 2797: 2794: 2791: 2787: 2784: 2778: 2775: 2770: 2766: 2762: 2758: 2754: 2750: 2743: 2740: 2735: 2731: 2727: 2723: 2719: 2715: 2714: 2706: 2703: 2698: 2694: 2690: 2686: 2682: 2678: 2671: 2669: 2665: 2660: 2656: 2651: 2646: 2642: 2638: 2634: 2627: 2625: 2623: 2621: 2619: 2617: 2613: 2608: 2604: 2599: 2594: 2590: 2586: 2582: 2575: 2572: 2567: 2563: 2559: 2555: 2551: 2547: 2544:(4): 259–96. 2543: 2539: 2532: 2530: 2528: 2526: 2522: 2516: 2513: 2508: 2504: 2500: 2496: 2492: 2488: 2485:(4): 253–65. 2484: 2480: 2473: 2471: 2469: 2467: 2465: 2463: 2459: 2454: 2450: 2446: 2442: 2438: 2434: 2431:(3): 264–73. 2430: 2426: 2419: 2417: 2415: 2413: 2409: 2404: 2400: 2396: 2392: 2388: 2384: 2377: 2375: 2373: 2371: 2369: 2367: 2365: 2363: 2361: 2359: 2355: 2350: 2346: 2342: 2338: 2334: 2330: 2323: 2321: 2319: 2317: 2315: 2313: 2311: 2309: 2305: 2300: 2296: 2291: 2286: 2282: 2278: 2274: 2267: 2265: 2263: 2261: 2259: 2257: 2253: 2240: 2236: 2230: 2227: 2214: 2210: 2204: 2201: 2188: 2184: 2178: 2176: 2172: 2165: 2160: 2157: 2155: 2152: 2150: 2147: 2145: 2142: 2140: 2137: 2135: 2132: 2130: 2127: 2125: 2122: 2120: 2117: 2115: 2112: 2110: 2107: 2105: 2102: 2100: 2097: 2095: 2092: 2090: 2087: 2085: 2082: 2080: 2077: 2075: 2072: 2070: 2067: 2065: 2062: 2061: 2057: 2049: 2046:December 2016 2037: 2032: 2023: 2022: 2016: 2013: 2009: 2006: 2002: 1999: 1994: 1990: 1986: 1985: 1984: 1977: 1975: 1971: 1969: 1968: 1963: 1959: 1955: 1951: 1950: 1944: 1942: 1938: 1934: 1933: 1928: 1920: 1918: 1912: 1908: 1904: 1901: 1898: 1895: 1891: 1888: 1884: 1883: 1879: 1877: 1875: 1870: 1866: 1862: 1857: 1850: 1848: 1845: 1841: 1833:Human factors 1832: 1828: 1827:neurotoxicity 1825: 1822: 1819: 1816: 1813: 1810: 1807: 1804: 1801: 1798: 1795: 1792: 1791: 1787: 1782: 1765: 1764: 1759: 1756: 1752: 1751: 1746: 1743: 1740: 1735: 1734: 1729: 1726: 1723: 1720: 1717: 1713: 1710: 1706: 1703: 1699: 1698: 1693: 1690: 1687: 1683: 1681: 1676: 1672: 1668: 1664: 1660: 1659: 1655: 1651: 1648: 1644: 1640: 1636: 1633: 1630: 1625: 1624:depsipeptides 1621: 1620: 1616: 1612: 1609: 1608: 1604: 1603: 1598: 1595: 1594: 1590: 1588: 1587: 1584: 1580: 1579: 1574: 1567: 1565: 1563: 1559: 1552: 1550: 1546: 1544: 1540: 1539: 1534: 1530: 1525: 1517: 1511: 1508: 1505: 1502: 1499: 1495: 1492: 1489: 1485: 1481: 1478: 1475: 1471: 1467: 1466: 1461: 1457: 1453: 1449: 1445: 1441: 1437: 1434: 1433: 1432: 1430: 1427: 1423: 1422: 1418: 1414: 1410: 1405: 1397: 1393: 1386: 1381: 1377: 1374: 1371: 1367: 1366:breast cancer 1363: 1359: 1355: 1352: 1351: 1350: 1348: 1344: 1340: 1336: 1335: 1330: 1326: 1321: 1313: 1308: 1302: 1295: 1291: 1287: 1284: 1280: 1279: 1276: 1271: 1266: 1262: 1258: 1254: 1251: 1247: 1244: 1240: 1236: 1233: 1229: 1225: 1221: 1220: 1217: 1212: 1207: 1203: 1199: 1195: 1192: 1188: 1185: 1181: 1177: 1174: 1170: 1166: 1162: 1161: 1155: 1154:Dolastatin 15 1150: 1149:Dolastatin 10 1146: 1142: 1138: 1135: 1131: 1128: 1124: 1123: 1120: 1115: 1110: 1106: 1102: 1098: 1095: 1091: 1088: 1084: 1083: 1080: 1075: 1070: 1066: 1062: 1058: 1055: 1051: 1048: 1044: 1040: 1033: 1025: 1022: 1020: 1017: 1016: 1013:Phases I–III 1012: 1009: 1007: 1004: 1003: 999: 996: 993: 990: 987: 986: 982: 979: 975: 972: 969: 966: 959: 955: 953:Solid tumours 952: 949: 948: 944: 941: 939: 936: 935: 931: 928: 926: 923: 922: 918: 915: 911: 907: 903: 901: 898: 894: 890: 887: 885: 884:Hemiasterlins 882: 881: 877: 873: 870: 868: 865: 864: 860: 857: 855: 854:Halichondrins 852: 851: 847: 845:Solid tumours 844: 842: 839: 838: 835: 832: 830: 829:breast cancer 826: 822: 819: 817: 814: 813: 809: 805: 801: 799: 795: 793: 790: 789: 785: 783: 779: 776: 774: 771: 770: 766: 763: 760: 758: 755: 748: 744: 741: 738: 735: 732: 731: 718: 713: 706: 701: 694: 689: 686: 684: 681: 675: 673: 671: 663: 661: 654: 652: 650: 645: 641: 636: 628: 626: 624: 620: 570: 566: 562: 558: 553: 549: 545: 542: 537: 529: 525: 523: 519: 515: 511: 510:deoxygenation 506: 498: 494: 490: 486: 478: 474: 472: 468: 463: 459: 455: 447: 440: 438: 436: 431: 427: 422: 418: 414: 410: 405: 401: 399: 394: 384: 380: 378: 374: 370: 366: 361: 359: 354: 350: 346: 342: 338: 334: 330: 325: 322: 299: 297: 293: 291: 287: 283: 279: 275: 271: 263: 261: 259: 255: 250: 248: 243: 237: 234: 230: 226: 218: 216: 214: 210: 206: 205:cell division 202: 198: 194: 188: 184: 177: 175: 173: 169: 165: 161: 157: 153: 149: 144: 142: 138: 134: 130: 126: 122: 118: 114: 110: 106: 101: 99: 95: 91: 87: 83: 79: 75: 71: 67: 63: 59: 55: 51: 47: 39: 34: 30: 19: 6369:tea tree oil 6354:lemon myrtle 6267:ethylparaben 6197:griseofulvin 6187: 6058:Benzylamines 5947:ravuconazole 5942:albaconazole 5934:voriconazole 5929:posaconazole 5919:itraconazole 5909:hexaconazole 5827:neticonazole 5817:luliconazole 5812:ketoconazole 5802:flutrimazole 5787:eberconazole 5777:clotrimazole 5762:butoconazole 5592: 5560: 5547:Topiroxostat 5541:Myo-inositol 5450:Atorvastatin 5252:Tazemetostat 5216:Alitretinoin 5209: 5120:Estramustine 5100:Elsamitrucin 5090:Eflornithine 5044:Pegaspargase 5040:Asparaginase 5033: 5002:Testolactone 4995: 4983: 4971: 4925: 4910:Panobinostat 4893: 4863: 4851: 4839: 4827: 4798: 4763: 4751: 4704: 4700:Padeliporfin 4639:Dactinomycin 4635:Streptomyces 4616:Temozolomide 4611:Mitozolomide 4599: 4590:Mitobronitol 4579:Procarbazine 4572: 4560:Nonclassical 4485: 4462: 4456:Streptozocin 4421:Nitrosoureas 4419: 4393:Chlorambucil 4387:Trofosfamide 4373:Chlormethine 4368:Bendamustine 4361: 4299:Mitoxantrone 4294:Losoxantrone 4287: 4247:Daunorubicin 4230: 4196: 4133:Camptothecin 4121: 4077: 4047: 4033: 4016: 4000:Fluorouracil 3980:Capecitabine 3973: 3943: 3907: 3893: 3863: 3858:Pralatrexate 3848:Methotrexate 3836: 3779: 3742: 3699: 3674: 3587: 3583: 3577: 3552: 3548: 3513:(2): 72–84. 3510: 3506: 3470: 3466: 3460: 3448:. Retrieved 3423: 3419: 3387: 3379:the original 3374: 3364: 3353: 3341:. Retrieved 3308: 3304: 3294: 3282:. Retrieved 3278: 3268: 3238:(3): 252–6. 3235: 3231: 3225: 3190: 3186: 3176: 3164:. Retrieved 3147: 3143: 3133: 3121:. Retrieved 3117:the original 3077: 3073: 3067: 3042: 3038: 3032: 3020:. Retrieved 2995: 2991: 2981: 2959:(1): 57–70. 2956: 2952: 2914: 2910: 2904: 2869: 2865: 2855: 2843:. Retrieved 2810: 2806: 2796: 2777: 2752: 2748: 2742: 2717: 2711: 2705: 2680: 2676: 2640: 2636: 2588: 2584: 2574: 2541: 2537: 2515: 2482: 2478: 2428: 2424: 2386: 2382: 2332: 2328: 2280: 2276: 2243:. Retrieved 2239:the original 2229: 2217:. Retrieved 2203: 2191:. Retrieved 2187:the original 2114:Cryptophycin 2084:Chemotherapy 2043: 2035: 1998:angiogenesis 1981: 1972: 1965: 1953: 1947: 1945: 1930: 1924: 1916: 1886: 1854: 1836: 1788:Side effects 1774:μM versus 23 1770:value of 3.0 1761: 1748: 1731: 1695: 1678: 1656: 1646: 1642: 1638: 1617: 1611:Cryptophycin 1600: 1586:microtubules 1576: 1573:Griseofulvin 1571: 1568:Griseofulvin 1556: 1547: 1536: 1527: 1463: 1419: 1407: 1332: 1327:are complex 1323: 1297:Epothilone B 1275:Epothilone A 1042:Vinca domain 956:Phase I, II 753:Vinca domain 682: 679: 669: 667: 658: 640:Cytogenetics 638: 635:Cytogenetics 557:fluorination 535: 534: 514:cytotoxicity 505:cyclopropane 484: 483: 467:heterocyclic 453: 452: 406: 402: 389: 362: 341:prometaphase 326: 321:dissociation 318: 294: 282:treadmilling 267: 251: 238: 222: 197:cytoskeleton 193:Microtubules 191: 178:Microtubules 172:griseofulvin 145: 102: 98:cytogenetics 86:cancer cells 74:microtubules 53: 49: 45: 43: 29: 6409:from market 6388:pentamidine 6349:lemon grass 6307:taurolidine 6277:polynoxylin 6178:flucytosine 6122:caspofungin 6046:terbinafine 6032:Allylamines 5894:fluconazole 5886:terconazole 5881:fluconazole 5852:tioconazole 5847:sulconazole 5837:oxiconazole 5832:omoconazole 5807:isoconazole 5782:croconazole 5740:inhibitors) 5738:demethylase 5695:Antifungals 5637:from market 5615:Pegloticase 5610:Rasburicase 5536:Phytic acid 5501:Allopurinol 5460:Guaifenesin 5455:Fenofibrate 5399:Uricosurics 5327:from market 5297:Vorasidenib 5277:Trabectedin 5262:Tiazofurine 5257:Tebentafusp 5242:Tagraxofusp 5200:Plitidepsin 5170:Mitoguazone 5110:Epacadostat 5080:Demecolcine 5024:Aflibercept 4997:Sex steroid 4870:Fuzuloparib 4811:Carfilzomib 4783:Palbociclib 4773:Abemaciclib 4726:Verteporfin 4690:Efaproxiral 4606:Dacarbazine 4568:Altretamine 4550:Satraplatin 4545:Oxaliplatin 4525:Carboplatin 4502:Triaziquone 4473:Mannosulfan 4451:Ranimustine 4431:Fotemustine 4272:Pirarubicin 4257:Doxorubicin 4251:+cytarabine 4237:Aclarubicin 4198:Podophyllum 4123:Camptotheca 4054:Azacitidine 4040:Gemcitabine 3995:Floxuridine 3928:Fludarabine 3923:Clofarabine 3909:Halogenated 3900:Pentostatin 3875:Raltitrexed 3843:Aminopterin 3786:Ixabepilone 3781:Epothilones 3749:Cabazitaxel 3726:Vinorelbine 3711:Vincristine 3706:Vinblastine 3691:microtubule 2755:(1): 1–12. 2335:(1): 1–17. 2149:Epothilones 2104:Vinorelbine 2099:Vincristine 2094:Vinblastine 2089:Drug design 2074:Microtubule 1992:inhibitors. 1954:Vinca rosea 1941:vincristine 1937:vinblastine 1906:resistance. 1869:xenobiotics 1820:hypotension 1783:Limitations 1745:Epothilones 1674:to tubulin. 1578:Penicillium 1504:Vinorelbine 1480:Vincristine 1470:hemostatics 1460:vincristine 1456:Vinblastine 1436:Vinblastine 1426:microtubule 1358:lung cancer 1343:microtubule 1238:TAXANE SITE 1079:Vinorelbine 1074:Vincristine 1069:Vinblastine 867:Dolastatins 798:lung cancer 792:Vinorelbine 773:Vincristine 757:Vinblastine 644:chromosomal 536:Vinblastine 497:specificity 398:instability 349:kinetochore 286:catastrophe 233:filamentous 229:heterodimer 209:chromosomes 164:vinorelbine 160:vincristine 156:vinblastine 94:metastasize 78:chromosomes 70:nail fungus 6440:Categories 6378:atovaquone 6359:orange oil 6322:tolnaftate 6317:tolciclate 6302:sulbentine 6272:haloprogin 6252:ciclopirox 6217:tavaborole 6209:inhibitors 6195:Systemic: 6176:Systemic: 6137:rezafungin 6132:micafungin 6127:cilofungin 6111:Systemic: 6105:inhibitors 6088:amorolfine 6067:butenafine 6024:inhibitors 6008:Systemic: 5985:ergosterol 5892:Systemic: 5822:miconazole 5772:climbazole 5757:bifonazole 5748:Imidazoles 5724:inhibitors 5721:Ergosterol 5585:Cinchophen 5569:Colchicine 5527:Febuxostat 5511:Tisopurine 5506:Oxypurinol 5445:Amlodipine 5414:Probenecid 5292:Verdinexor 5287:Venetoclax 5190:Oblimersen 5185:Navitoclax 5160:Lucanthone 5155:Lonidamine 5145:Lifileucel 5140:Ivosidenib 5135:Imetelstat 5105:Enasidenib 5095:Elesclomol 5060:Bexarotene 5055:Belzutifan 4990:Bexarotene 4978:Atrasentan 4953:Umbralisib 4948:Idelalisib 4938:Copanlisib 4920:Vorinostat 4915:Romidepsin 4905:Entinostat 4900:Belinostat 4858:Masoprocol 4846:Tiazofurin 4834:Anagrelide 4806:Bortezomib 4793:Seliciclib 4788:Ribociclib 4768:inhibitors 4758:Tipifarnib 4721:Temoporfin 4716:Talaporfin 4654:Plicamycin 4649:Mitomycins 4595:Pipobroman 4574:Hydrazines 4540:Nedaplatin 4492:Carboquone 4487:Aziridines 4478:Treosulfan 4426:Carmustine 4413:Uramustine 4382:Ifosfamide 4354:Alkylating 4315:Bisantrene 4304:Pixantrone 4277:Valrubicin 4267:Idarubicin 4262:Epirubicin 4208:Teniposide 4163:Lurtotecan 4158:Irinotecan 4059:Decitabine 4023:Cytarabine 3966:Pyrimidine 3955:Tioguanine 3945:Thiopurine 3934:Nelarabine 3918:Cladribine 3870:Pemetrexed 3853:Pemetrexed 3829:Folic acid 3769:Paclitaxel 3721:Vinflunine 3450:21 January 3426:: 615–27. 3343:21 January 3284:26 October 3166:21 January 2845:21 January 2166:References 2144:Paclitaxel 2124:Colchicine 2109:Vinflunine 1962:paclitaxel 1728:Paclitaxel 1680:Cymbastela 1671:cell lines 1529:Colchicine 1524:Colchicine 1518:Colchicine 1510:Vinflunine 1354:Paclitaxel 1270:Paclitaxel 1206:Colchicine 1109:Vinflunine 1006:Epothilone 991:(Taxotere) 968:Paclitaxel 964:Taxan site 908:diseases ( 906:neoplastic 900:Colchicine 878:completed 816:Vinflunine 518:equipotent 485:Paclitaxel 473:compound. 454:Colchicine 435:tumor cell 430:activation 426:hydrolysis 413:nucleation 409:paclitaxel 373:paclitaxel 329:cell cycle 168:Colchicine 148:paclitaxel 129:cell cycle 84:, because 38:paclitaxel 6419:Phase III 6407:Withdrawn 6364:patchouli 6312:ticlatone 6215:Topical: 6086:Topical: 6065:Topical: 6041:naftifine 6039:Topical: 6012:, hamycin 6000:natamycin 5993:Topical: 5966:abafungin 5964:Topical: 5957:Thiazoles 5940:Unknown: 5874:Topical: 5867:Triazoles 5792:econazole 5755:Topical: 5647:Phase III 5635:Withdrawn 5601:Sevelamer 5532:Inositols 5465:Lesinurad 5438:secondary 5337:Phase III 5325:Withdrawn 5302:Vosaroxin 5282:Veliparib 5237:Sotorasib 5227:Selinexor 5221:Tretinoin 5211:Retinoids 5125:Glasdegib 5070:Celecoxib 5019:Adagrasib 4943:Duvelisib 4933:Alpelisib 4888:Rucaparib 4875:Niraparib 4816:Oprozomib 4778:Alvocidib 4644:Bleomycin 4601:Triazenes 4585:Etoglucid 4530:Cisplatin 4446:Nimustine 4440:Semustine 4436:Lomustine 4398:Melphalan 4325:Menogaril 4320:Crisnatol 4310:Amsacrine 4282:Zorubicin 4242:Amrubicin 4203:Etoposide 4178:Topotecan 4173:Silatecan 4168:Rubitecan 4153:Gimatecan 4138:Cositecan 4128:Belotecan 3804:inhibitor 3774:Tesetaxel 3764:Ortataxel 3759:Larotaxel 3754:Docetaxel 3716:Vindesine 3187:Pharm Res 2139:Docetaxel 2008:Liposomes 1722:Docetaxel 1562:may apple 1494:Vindesine 1440:leukaemia 1376:Docetaxel 1265:Docetaxel 989:Docetaxel 874:Phase I; 834:Phase III 782:lymphomas 569:alkaloids 377:mechanism 358:apoptosis 345:metaphase 339:. During 219:Structure 152:docetaxel 105:alkaloids 6262:dimazole 6005:nystatin 5987:binding) 5713:membrane 5470:Losartan 5175:Mitotane 5115:Eribulin 4883:Olaparib 4821:Ixazomib 4497:Thiotepa 4469:Busulfan 4148:Exatecan 3985:Carmofur 3693:assembly 3656: / 3612:19282719 3604:18158980 3569:10395834 3527:16545633 3487:18220536 3444:Archived 3440:11818492 3396:Archived 3337:Archived 3325:12587805 3252:12010611 3217:22814904 3160:Archived 3156:12748304 3123:5 August 3094:10092957 3059:16296875 3016:Archived 2973:18666378 2931:14987065 2896:19125622 2839:Archived 2786:Archived 2769:15638787 2734:12769688 2697:19817710 2659:19010832 2607:14663486 2585:Oncogene 2566:32194348 2507:10228718 2499:15057285 2453:45866448 2445:15948296 2403:15579115 2349:12678749 2299:19671735 2245:5 August 2219:5 August 2213:Archived 2193:5 August 2159:eribulin 2058:See also 1887:in vitro 1823:alopecia 1654:sea hare 1533:alkaloid 1498:melanoma 1484:lymphoma 1329:terpenes 1026:Phase I 995:Prostate 945:Phase I 932:Phase I 891:Phase I 876:phase II 861:Phase I 778:Leukemia 572:L-trp-OC 552:skeletal 489:efficacy 458:toxicity 353:anaphase 333:prophase 242:polarity 137:oncology 113:monomers 109:polymers 6446:Mitosis 6383:dapsone 5995:hamycin 5596:aspirin 5407:primary 4104:S phase 4005:Tegafur 3819:S phase 3744:Taxanes 3680:M phase 3333:1541302 3260:4507579 3208:3667160 3012:7603142 2887:2765517 2827:8656780 2558:9664292 2069:Tubulin 2036:updated 1958:taxanes 1663:mollusc 1325:Taxanes 1320:Taxanes 1314:Taxanes 974:Ovarian 970:(Taxol) 821:Bladder 804:phase I 623:prodrug 561:in vivo 522:oxetane 462:tropone 280:' and ' 274:dynamic 133:taxanes 125:tubulin 121:mitosis 117:tubulin 58:mitosis 6402:WHO-EM 6230:Others 6080:Others 5732:Azoles 5630:WHO-EM 5593:except 5590:NSAIDs 5320:WHO-EM 4929:(Pi3K) 3886:Purine 3689:Block 3610: 3602: 3567: 3525: 3485: 3438: 3331: 3323: 3258: 3250: 3215: 3205: 3154: 3092: 3057: 3022:5 July 3010: 2992:Lancet 2971: 2929: 2894: 2884: 2835:647015 2833: 2825: 2767: 2732: 2695: 2657: 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