Bafilomycin - Knowledge (XXG)

780:, meaning it can transfer K ions across biological membranes. Typically, the mitochondrial inner membrane is not permeable to K and maintains a set electrochemical gradient. In excitable cells, mitochondria can contain a K channel that, when opened, can cause mitochondrial stress by inducing mitochondrial swelling, changing the electrochemical gradient, and stimulating respiration. Bafilomycin A1 treatment can induce mitochondrial swelling in the presence of K ions, stimulate the oxidation of pyrimidine nucleotides and uncouple 194: 921:(IBM) is relatively common in patients over 50 years of age and involves over activation of autophagic flux. In this condition, increased autophagy results in an increase in protein degradation and therefore an increase in the presentation of antigenic peptides in muscles. This can cause over-activation of immune cells. Treatment with bafilomycin can prevent the acidification of lysosomes and therefore autophagy, decreasing the number of antigenic peptides digested and displayed to the immune system. 439: 700:. Autophagosomes then fuse with lysosomes facilitating the degradation of engulfed cargo by lysosomal proteases. This process is critical in maintaining the cell's store of amino acids and other nutrients during times of nutrient deprivation or other metabolic stresses. Bafilomycin interferes with this process by inhibiting the acidification of the lysosome through its interaction with V-ATPase. Lack of lysosomal acidification prevents the activity of lysosomal proteases like 597:(a3) and renal intercalated cells (a4). If located at the lysosomal membrane, this results in the acidification of the lysosome as lumenal pH is lowered, enabling activity of lysosomal hydrolases. When V-ATPase is located at the plasma membrane, proton extrusion through the pump causes the acidification of the extracellular space, which is utilized by specialized cells such as osteoclasts, epididymal clear cells, and renal epithelial intercalated cells. 708: 467:(ATP) hydrolysis to pump protons across a biological membrane. When bafilomycin and other inhibitors of V-ATPase, such as concanamycin, were first discovered in the 1980s they were used to establish the presence of V-ATPase in specialized cells types and tissues, characterizing the proton pump's distribution. Structurally, V-ATPase consists of 13 distinct subunits that together make up the membrane spanning V 1018:, displayed an increased effect when administered after bafilomycin treatment. With bafilomycin, faster contraction and relaxation of the aorta was seen as bafilomycin prevented the ion trapping of xylometazoline in the lysosome. Without pre-treatment with bafilomycin, the functional V-ATPase causes the lysosome to become a reservoir for xylometazoline, slowing its effect on contractility. 37: 989: 452: 284: 949:

autophagy is stimulated, bafilomycin blocks its final stage of autophagosome-lysosomal fusion resulting in the accumulation of autophagosomes. Levels of autophagy related proteins associated with autophagosomes, such as LC3, can then be monitored to determine the level of autophagosome formation induced by nutrient deprivation.

973:, are known as lysosomotropic drugs. These drugs are weak bases that become protonated in the acidic environment of the lysosome. This traps the otherwise non-protonated compound within the lysosome, as protonation prevents its passage back across the lipid membrane of the organelle. This phenomenon is known as 948:

Bafilomycin is commonly used to study this autophagic flux in neurons, among other cell types. To do this, neurons are first put into nutrient rich conditions then into nutrient starved conditions to stimulate autophagy. Bafilomycin is co-administered in the condition of nutrient stress so that while

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exports a membrane network into the red blood cell cytoplasm and also inserts several of its own proteins into the host membrane, including its own V-ATPase. This proton pump has a role in maintaining the intracellular pH of the infected red blood cell and facilitating the uptake of small metabolites

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With its role in lysosomal acidification, V-ATPase is also crucial in driving the transport of ions and small molecules into the cytoplasm, particularly calcium and amino acids. Additionally, its acidification of endosomes is critical in receptor endocytosis as low pH tends to drive ligand release as

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Pérez-Vargas J, Shapira T, Olmstead AD, Villanueva I, Thompson CA, Ennis S, Gao G, De Guzman J, Williams DE, Wang M, Chin A, Bautista-Sánchez D, Agafitei O, Levett P, Xie X, Nuzzo G, Freire VF, Quintana-Bulla JI, Bernardi DI, Gubiani JR, Suthiphasilp V, Raksat A, Meesakul P, Polbuppha I, Cheenpracha

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typically display elevated levels of protein aggregates within the cell that contribute to dysfunction of neurons and eventual neuronal death. As a method of protein degradation within the cell, autophagy can traffic these protein aggregates to be degraded in the lysosome. Although it is unclear the

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V-ATPase dysregulation is thought to play a role in resistance to cancer therapies, as aberrant acidification of the extracellular environment can protonate chemotherapeutics, preventing their entry into the cell. It is unclear if` V-ATPase dysregulation is a direct cause of associated poor clinical

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following a 12-24 hour treatment with 100 or 400 nM Bafilomycin. However, further studies have failed to see this inhibition of fusion with similar bafilomycin treatments. These contradictory results have been explained by time differences among treatments as well as use of different cell lines. The

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c subunit. These data suggested that the bafilomycin binding site was on the outer surface of the Vo domain, at the interface between two c subunits. This binding site has recently been described in high resolution by two groups that used cryo electron microscopy to obtain structures of the V-ATPase

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domain. It was further found that amino acid changes within subunit a could also lower V-ATPase-Bafilomycin interaction, indicating a minor role of subunit a in bafilomycin binding in addition to subunit c. An analysis of nine mutations that conferred resistance to bafilomycin showed all of them to

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As a lysosomotropic drug, chloroquine typically accumulates in the lysosome disrupting their degradative function, inhibiting autophagy, and inducing apoptosis through Bax-dependent mechanisms. However, in cultured cerebellar granule neurons (CGNs) low treatment with Bafillomycin of 1 nM decreased

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and increased expression of HIF1alpha. These effects suggest that inhibition of V-ATPase with bafilomycin can induce a cellular stress response, including autophagy and eventual apoptosis. These somewhat contradictory effects of V-ATPase inhibition in terms of inhibition or induction of apoptosis

593:. In mammals, location of the V-ATPase can be linked to the specific isoform of subunit a that the complex has. Isoforms a1 and a2 target V-ATPase intracellularly, to synaptic vesicles and endosomes respectively. Subunits a3 and a4, however, mediate V-ATPase localization to the plasma membrane in 647:

When at the plasma membrane, V-ATPase function is critical in the acidification of the extracellular environment, which is seen with osteoclasts and epididymal clear cells. When present at the plasma membrane in renal epithelial intercalated cells, V-ATPase is important for acid secretion, which

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When one of these drugs is co-applied to cells with bafilomycin A1, the action of bafilomycin A1 prevents the acidification of the lysosome, therefore preventing the phenomenon of ion trapping in this compartment. As the lysosome cannot acidify, lysosomotropic drugs do not become protonated and

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patients, the autophagy pathway has been found to be altered in both B and T cells. Particularly, more autophagic vacuoles were seen in T cells as well as increased LC3-11 staining for autophagosomes, indicating increased autophagy. Increased autophagy can also be seen in naïve patient B cell

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subunit a could restore function. This suggested bafilomycin interacted specifically with subunit a of V-ATPase; however, another study contradicted this finding. A group found that by using a bafilomycin affinity chromatography column V-ATPase could be purified, and that addition of DCCD, an

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c subunit of the V-ATPase complex and inhibits proton translocation. Although the interaction between bafilomycin and V-ATPase is not covalent, its low dissociation constant of about 10 nM describes the strength of its interaction and can make the effects of bafilomycin difficult to reverse.

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domain of the enzyme, enabling both the rotation of the central stalk of the pump, made up of subunits D, F and d, and the rotation of the proteolipid ring. This rotation puts the protonated glutamic acid residues in contact with a luminal hemichannel located in subunit a. Within subunit a,

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In addition to blocking the acidification of the lysosome, Bafilomycin has been reported to block the fusion of autophagosomes with lysosomes. This was initially found in a paper by Yamamoto, et al. in which the authors used bafilomycin A1 to treat rat hepatoma H-4-II-E cells. By

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Diagram showing how protonation of weak bases like chloroquine in the acidic environment of the lysosome results in ion trapping, or accumulation of the weak base in the lysosome. Bafilomycin inhibits this trapping through its action on V-ATPase, which normally acidifies the

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Since V-ATPase is widely distributed within the cell, Bafilomycin is only specific as an autophagy inhibitor for a short amount of time. Other effects are seen outside this short window, including interference in the trafficking of endosomes and proteasomal inhibition.

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chloroquine induced apoptosis without affecting chloroquine inhibition of autophagy. The exact mechanism of this protection is unknown, although it is hypothesized to lie downstream of autophagosome-lysosome fusion yet upstream of Bax induction of apoptosis.

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S, Jaidee W, Kanokmedhakul K, Yenjai C, Chaiyosang B, Teles HL, Manzo E, Fontana A, Leduc R, Boudreault PL, Berlinck RG, Laphookhieo S, Kanokmedhakul S, Tietjen I, Cherkasov A, Krajden M, Nabi IR, Niikura M, Shi PY, Andersen RJ, Jean F (January 2023).

728:, they saw a blockage of autophagosome-lysosome fusion after using bafilomycin at a concentration of 100 nM for 1 hour. This has been confirmed by other studies, particularly two that found decreased colocalization of mitochondria and lysosomes by 808:

The mechanism by which bafilomycin causes this cancer specific anti-proliferative effect is multifactorial. In addition to the induction of caspase-dependent apoptosis through the mitochondrial pathway, bafilomycin also causes increased levels of

784:. Ascending concentrations of bafilomycin were found to linearly increase the amount of K that traversed the mitochondrial membrane, confirming it acts as an ionophore. Compared to other ionophores, however, bafilomycin has a low affinity for K. 668:, and renal acidosis. Additionally, V-ATPase can be found at the plasma membrane of some invasive cancer cells including breast, prostate and liver cancer, among others. In human lung cancer samples, V-ATPase expression was correlated with 525:

For more than ten years after bafilomycin was discovered as a V-ATPase inhibitor, the site of its interaction with V-ATPase was unclear. Beginning studies used the chromaffin granule V-ATPase to suggest that bafilomycin interacted with the

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resistant cells, V-ATPase expression was found to be increased, and co-treatment of bafilomycin with cisplatin sensitized these cells to cisplatin-induced cytotoxicity. Bafilomycin has also been shown to increase the efficacy of

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As one of the first identified and most commonly used, bafilomycin A1 is of particular importance, especially as its structure serves as the core of all other bafilomycins. With its large structure, bafilomycin has multiple

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Pretreating cells with bafilomycin before administration of a cationic drug can alter the kinetics of the cationic compound. In a rabbit contractility assay, bafilomycin was used to pre-treat isolated rabbit

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Marceau F, Bawolak MT, Lodge R, Bouthillier J, Gagné-Henley A, Gaudreault RC, Morissette G (February 2012). "Cation trapping by cellular acidic compartments: beyond the concept of lysosomotropic drugs".

740:, an increase in the autophagosome marker LC3-II has been seen with Bafilomycin treatment. This occurs as autophagosomes fail to fuse with lysosomes, which normally stimulates the degradation of LC3-II. 648:

contributes to the acidification of urine. In response to reduced plasma pH, increased levels of V-ATPase are typically trafficked to the plasma membrane in these cells by phosphorylation of the pump by

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residues serve to stabilize the deprotonated form of glutamic acid and allow the release of their protons. This rotation and proton transfer brings the protons through the pump and across the membrane.

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bafilomycin's anti-proliferative effect appears to be specific to cancer cells over normal cells, which is seen with selective inhibition of hepatoblastoma cell growth compared to healthy hepatocytes.

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exact role continuous autophagy, or autophagic flux, plays in neuronal homeostasis and disease states, it has been shown that autophagic dysfunction can be seen in neurodegenerative diseases.

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and reduced clinical outcome. Bafilomycin application has been shown to reduce cell growth in various cancer cell lines across multiple cancer types by induction of apoptosis. Additionally,

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Saris NE, Andersson MA, Mikkola R, Andersson LC, Teplova VV, Grigoriev PA, Salkinoja-Salonen MS (August 2009). "Microbial toxin's effect on mitochondrial survival by increasing K+ uptake".

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at equilibrium. Treatment of the parasitized red blood cell with bafilomycin prevents the extracellular acidification, causing a dip in intracellular pH around the malarial parasite.

3294: 3274: 2773: 297: 3967: 3971: 3963: 2766: 1207:"Vacuolar H(+)-ATPase localized in plasma membranes of malaria parasite cells, Plasmodium falciparum, is involved in regional acidification of parasitized erythrocytes" 797:

In many cancers, it has been found that various subunits of V-ATPase are upregulated. Upregulation of these subunits appears to be correlated with increased tumor cell

828:, bafilomycin also caused tumor regression in MDA-MB-231 xenograft mice. In a HepG2 orthotropic HCC xenograft model in nude mice, bafilomycin prevented tumor growth. 408:

and shown to have antibiotic activity against some yeast, Gram-positive bacteria and fungi. Bafilomycin A1 was also shown to have an anti-proliferative effect on

3390: 3385: 334:, including anti-tumor, anti-parasitic, immunosuppressant and anti-fungal activity. The most used bafilomycin is bafilomycin A1, a potent inhibitor of cellular 3263: 2937: 2269:

Lumkwana D, du Toit A, Kinnear C, Loos B (June 2017). "Autophagic flux control in neurodegeneration: Progress and precision targeting-Where do we stand?".

764:, which is an initiator of apoptosis. Bafilomycin has also been shown to induce both inhibition of autophagy and subsequent induction of apoptosis in 551:

c subunit, drastically decreased bafilomycin's affinity for V-ATPase. This suggested that bafilomycin interacted more strongly with subunit c of the V

852:(ABC) transporters. These transporters are identified as good anti-fungal targets as they render organisms unable to cope with cation stress. When 814:

demonstrate that bafilomycin's function is critically dependent on cellular context, and can mediate either a pro-survival or pro-death phenotype.

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and functional groups, which makes modifying its structure difficult, a task that has been attempted to reduce the compound's associated toxicity.

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As the target of Bafilomycin V-ATPase, is involved in many aspects of cellular function, Bafilomycin treatment greatly alters cellular processes.

419:. In 2010, 9-hydroxy-bafilomycin D, 29-hydroxy-bafilomycin D and a number of other bafilomycins were identified from the endophytic microorganism 3683: 353:(V-ATPase) enzyme, a membrane-spanning proton pump that acidifies either the extracellular environment or intracellular organelles such as the 3637: 3523: 3448: 3420: 3080: 3344: 998:

subsequently trapped in the lysosome in the presence of bafilomycin. Additionally, when cells are preloaded with lysosomotropic drugs

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Vinod V, Padmakrishnan CJ, Vijayan B, Gopala S (April 2014). "'How can I halt thee?' The puzzles involved in autophagic inhibition".

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As it promotes the acidification of lysosomes, endosomes, and secretory vesicles, V-ATPase contributes to processes including:

977:. Trapping of the cationic compound also draws water into the lysosome through an osmotic effect, which can sometimes lead to 1812:"The bafilomycin/concanamycin binding site in subunit c of the V-ATPases from Neurospora crassa and Saccharomyces cerevisiae" 2646:

Muller S, Brun S, René F, de Sèze J, Loeffler JP, Jeltsch-David H (August 2017). "Autophagy in neuroinflammatory diseases".

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well as receptor cleavage which contributes to signaling events, such as through the release of the intracellular domain of

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domain to the coated vesicles. Further narrowing bafilomycin's interaction site, they found that specific addition of just V

89:)-16- -2- hydroxy-1-methylbutyl]-8-hydroxy-3,15- dimethoxy-5,7,9,11-tetramethyl-1- oxacyclohexadeca-3,5,11,13-tetraen-2-one 1002:, then treated with bafilomycin, bafilomycin acts to release the cationic compound from its accumulation in the lysosome. 577:

V-ATPase is ubiquitous in mammalian cells and plays an important role in many cellular processes. It is localized to the

304: 4026: 3959: 3836: 3335: 3249: 2812: 1861:"A model for the proteolipid ring and bafilomycin/concanamycin-binding site in the vacuolar ATPase of Neurospora crassa" 925: 660:

Clinically, dysfunction of V-ATPase has been correlated with several diseases in humans. Some of these diseases include

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Kuzu OF, Toprak M, Noory MA, Robertson GP (March 2017). "Effect of lysosomotropic molecules on cellular homeostasis".

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Duffy A, Le J, Sausville E, Emadi A (March 2015). "Autophagy modulation: a target for cancer treatment development".

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outcome or if its dysregulation primarily effects the response to treatment. Although treatment with bafilomycin and

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of animal cells or the vacuole of plants and fungi. At higher micromolar concentrations, bafilomycin A1 also acts on

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Within the cell, bafilomycin A1 specifically interacts with the proton pump V-ATPase. This large protein depends on

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Li Z, Du L, Zhang W, Zhang X, Jiang Y, Liu K, Men P, Xu H, Fortman JL, Sherman DH, Yu B, Gao S, Li S (April 2017).

941: 330:. Their chemical structure is defined by a 16-membered lactone ring scaffold. Bafilomycins exhibit a wide range of 2546:

Icho S, Rujas E, Muthuraman K, Tam J, Liang H, Landreth S, Liao M, Falzarano D, Julien JP, Melnyk RA (July 2022).

3478: 3144: 2548:"Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells" 824:

mouse models by 50% and did not show toxic effects at a dosing of 1 mg/kg. Additionally, when combined with

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in 1983. During a screen seeking to identify microbial secondary metabolites whose activity mimicked that of two

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Dröse S, Altendorf K (January 1997). "Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases".

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Ravanan P, Srikumar IF, Talwar P (November 2017). "Autophagy: The spotlight for cellular stress responses".

2491:"In silico screening of potent inhibitors against COVID-19 key targets from a library of FDA-approved drugs" 1440:"Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells" 918: 854: 810: 729: 636: 397: 672:. A large number of V-ATPase subunit mutations have also been identified in a number of cancers, including 189: 3894: 3856: 3533: 3400: 3116: 2789: 504: 464: 392: 3563: 3428: 2963: 2837: 131: 3776: 3753: 3327: 3324: 2804: 2438:

Zhang C, Wei B, Liu Z, Yao W, Li Y, Lu J, Ge C, Yu X, Li D, Zhu Y, Shang C, Jin N, Li X (January 2023).

1499:"Inhibitory effect of modified bafilomycins and concanamycins on P- and V-type adenosinetriphosphatases" 876: 733:

effect of Bafilomycin on autophagosome-lysosome fusion is complex and time dependent in each cell line.

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is the process by which the cell degrades its own organelles and some proteins through the formation of

321: 49: 3793: 3553: 3991: 3871: 3627: 3174: 3106: 2502: 2093: 1921: 1451: 1396: 378: 3578: 438: 4021: 3927: 3861: 3816: 3734: 3412: 3111: 3047: 821: 725: 673: 620: 331: 101: 3538: 1975:"Cryo-EM of the Yeast VO Complex Reveals Distinct Binding Sites for Macrolide V-ATPase Inhibitors" 1155:"Vacuolar ATPase as a potential therapeutic target and mediator of treatment resistance in cancer" 3884: 3375: 2897: 2709: 2294: 2202: 2010: 1420: 582: 3889: 3622: 3558: 3286: 858:

was treated with bafilomycin, growth inhibition was observed. Bafilomycin has also been used in

2917: 1611:"Autophagy, bafilomycin and cell death: the "a-B-cs" of plecomacrolide-induced neuroprotection" 368:

research applications; however, its clinical use is limited by a substantial toxicity profile.

4011: 3486: 3468: 3169: 2744: 2701: 2663: 2628: 2577: 2528: 2471: 2420: 2370: 2335: 2286: 2246: 2194: 2159: 2119: 2058: 2048: 2002: 1994: 1955: 1937: 1890: 1882: 1841: 1833: 1792: 1732: 1684: 1632: 1584: 1526: 1518: 1479: 1412: 1362: 1352: 1324: 1272: 1228: 1184: 1106: 756:, or programmed cell death. Additionally, in some cell lines it has been found to disrupt the 455:

Depiction of the molecular subunits that make up V-ATPase, the main target of Bafilomycin A1.

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In order to move protons across the membrane, a proton first enters subunit a within the V

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Bafilomycins have been shown to inhibit plasma membrane ATPase (P-ATPase) as well as the

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Weber SM, Levitz SM, Harrison TS (August 2000). "Chloroquine and the fungal phagosome".

2097: 1925: 1455: 1400: 1043:(MMP) levels by depressing Bcl-xL's mitochondrial protective role. Additionally, within 3932: 3607: 3548: 3052: 2993: 2983: 2958: 2892: 2623: 2596: 2572: 2547: 2523: 2490: 2466: 2439: 2415: 2390: 1950: 1909: 1787: 1762: 1679: 1654: 1653:

Yu Z, Zhao LX, Jiang CL, Duan Y, Wong L, Carver KC, Schuler LA, Shen B (January 2011).

1579: 1552: 1319: 1294: 1179: 1154: 1011: 881: 749: 628: 432: 409: 396:, ticks, and tapeworms, in addition to stimulating the release of γ-aminobutyruc acid ( 275: 2366: 2044: 1474: 1439: 1349:

Antimicrobial drug resistance handbook. Volume 2, Clinical and epidemiological aspects

707: 412:-stimulated T cells. However, its high toxicity has prevented use in clinical trials. 3985: 3940: 3851: 3785: 3602: 3568: 3453: 3380: 3362: 3199: 3179: 3131: 3070: 3060: 2882: 2713: 2489:

Elmorsy MA, El-Baz AM, Mohamed NH, Almeer R, Abdel-Daim MM, Yahya G (February 2022).

2014: 1251:"A malaria parasite-encoded vacuolar H(+)-ATPase is targeted to the host erythrocyte" 978: 697: 665: 496: 358: 343: 326: 182: 2440:"Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model" 2406: 2314:"Bafilomycin A1 inhibits autophagy and induces apoptosis in MG63 osteosarcoma cells" 2282: 2206: 1424: 215: 3164: 2862: 2298: 974: 765: 761: 712: 2953: 2842: 1205:

Hayashi M, Yamada H, Mitamura T, Horii T, Yamamoto A, Moriyama Y (November 2000).

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domain. Two further studies confirmed this hypothesis using V-ATPase from bovine

3826: 3655: 3650: 3632: 3491: 3395: 3357: 3228: 3220: 2998: 966: 930: 863: 837: 615: 401: 2697: 2514: 2456: 2391:"Discovery of lead natural products for developing pan-SARS-CoV-2 therapeutics" 2155: 2105: 1990: 1933: 1778: 1763:"Recent Insights into the Structure, Regulation, and Function of the V-ATPases" 1655:"Bafilomycins produced by an endophytic actinomycete Streptomyces sp. YIM56209" 1497:

Dröse S, Bindseil KU, Bowman EJ, Siebers A, Zeeck A, Altendorf K (1993-04-20).

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Proceedings of the National Academy of Sciences of the United States of America

3597: 3320: 3189: 3184: 3153: 3139: 3121: 3003: 2912: 2872: 2847: 2797: 2740: 2190: 2114: 970: 906: 898: 798: 594: 255: 142: 17: 1998: 1941: 1886: 1837: 1522: 1408: 1366: 534:. They showed that application of bafilomycin inhibited proton flow through V 3821: 3612: 3317: 3126: 2988: 2927: 1569: 1464: 1072: 1044: 833: 825: 777: 753: 701: 693: 339: 335: 36: 2748: 2705: 2667: 2632: 2595:

Sabino C, Basic M, Bender D, Elgner F, Himmelsbach K, Hildt E (June 2019).

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and the cellular organelles that are derived from it, including lysosomes,

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Bafilomycin A1 and bafilomycin D have shown antiviral properties against

586: 513: 404:. Independently, bafilomycin A1 and other derivatives were isolated from 354: 350: 162: 2225:"Does bafilomycin A1 block the fusion of autophagosomes with lysosomes?" 1670: 1514: 1102: 905:. Bafilomycin A1 has also demonstrated antiviral properties against the 171: 2978: 2867: 1973:

Keon KA, Benlekbir S, Kirsch SH, Müller R, Rubinstein JL (2022-03-18).

1727: 1710: 1295:"Immune and myodegenerative pathomechanisms in inclusion body myositis" 451: 423:

YIM56209. From 2004 to 2011, bafilomycins F-K were isolated from other

342:, transporting potassium K+ across biological membranes and leading to 202: 2613: 2241: 2224: 1627: 1610: 1170: 479:

domain in the cytosol is made up of subunits A through H whereas the V

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Marchesini N, Vieira M, Luo S, Moreno SN, Docampo R (November 2005).

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Bafilomycin A1 is most known for its use as an autophagy inhibitor.

386:, bafilomycin C1 was identified as an inhibitor of P-ATPase with a k 274:

Except where otherwise noted, data are given for materials in their

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Klionsky DJ, Elazar Z, Seglen PO, Rubinsztein DC (October 2008).

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subsets. Bafilomycin A1 treatment lowered the differentiation of

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bafilomycin reduced average tumor volume in MCF-7 and MDA-MB-231

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domain through a cytoplasmic hemichannel. This allows conserved

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and that this inhibition could be overcome by adding back the V

3684: 2597:"Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection" 866:

inhibitor FK506, displaying synergistic anti-fungal activity.

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Two years later, bafilomycins D and E were also isolated from

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Wang R, Wang J, Hassan A, Lee CH, Xie XS, Li X (2021-03-19).

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Clearance of protein aggregates in neurodegenerative diseases

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Overall, bafilomycin binds with nanomolar efficiency to the V

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Weisz OA (2003-01-01). "Acidification and protein traffic".

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of 11 μM. Bafilomycin C1 was found to have activity against

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Bafilomycin A1 serves as an important tool compound in many

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Environmental Science and Pollution Research International

1910:"Molecular basis of V-ATPase inhibition by bafilomycin A1" 1859:

Bowman BJ, McCall ME, Baertsch R, Bowman EJ (2006-10-20).

1810:

Bowman EJ, Graham LA, Stevens TH, Bowman BJ (2004-08-06).

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Cotter K, Stransky L, McGuire C, Forgac M (October 2015).

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Whitton B, Okamoto H, Packham G, Crabb SJ (August 2018).

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Xie Z, Xie Y, Xu Y, Zhou H, Xu W, Dong Q (August 2014).

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Bafilomycin has been shown to potentiate the effect of

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Chemical structures of several Bafilomycin compounds.

880:, the causative agent of malaria. Upon infection of 3908: 3870: 3802: 3762: 3715: 3682: 3673: 3500: 3343: 3334: 3219: 3212: 3079: 3025: 3016: 2943:

Tooltip Vesicular inhibitory amino acid transporter

2936: 2820: 2811: 1438:Bowman EJ, Siebers A, Altendorf K (November 1988). 459:: NOchotny at the English language Knowledge (XXG). 376:Bafilomycin A1, B1 and C1 were first isolated from 3717: 704:so that engulfed cargo can no longer be degraded. 483:domain is made up of subunits a, d, e, c, and c". 361:, which have a phosphorylated transitional state. 1244: 1242: 715:and the points of intervention of bafilomycin A1. 3764: 2264: 2262: 2260: 2218: 2216: 874:Bafilomycin has been shown to be active against 214: 3910: 3804: 3027: 2078: 2076: 2074: 2072: 1293:Keller CW, Schmidt J, Lünemann JD (June 2017). 1148: 1146: 1144: 1142: 1140: 110: 3689:Tooltip Glutamine aminohydrolase (glutaminase) 1756: 1754: 1752: 1750: 1748: 1746: 1711:"Inhibitors of V-ATPases: old and new players" 1604: 1602: 1600: 1598: 1299:Annals of Clinical and Translational Neurology 1200: 1198: 1138: 1136: 1134: 1132: 1130: 1128: 1126: 1124: 1122: 1120: 760:of the mitochondria and induce the release of 338:. Bafilomycins have also been found to act as 3302: 2774: 2137: 2135: 2133: 2026: 2024: 1342: 1340: 1338: 1288: 1286: 8: 3872: 2679: 2677: 1704: 1702: 1700: 1698: 1382: 1380: 1378: 1376: 1084: 1082: 1080: 2790: 711:Schematic representing the formation of an 3968:Metabotropic glutamate receptor modulators 3679: 3350:Tooltip Excitatory amino acid transporters 3340: 3309: 3295: 3287: 3216: 3022: 2817: 2781: 2767: 2759: 1648: 1646: 1546: 1544: 1542: 1540: 768:cells as well as other cancer cell lines. 192: 150: 28: 3275:Glutamate metabolism/transport modulators 2622: 2612: 2571: 2522: 2465: 2455: 2414: 2329: 2240: 2113: 1949: 1876: 1827: 1786: 1726: 1678: 1626: 1578: 1568: 1473: 1463: 1318: 1266: 1222: 1178: 499:residues within the proteolipid ring of V 3972:GABA metabolism and transport modulators 3964:Ionotropic glutamate receptor modulators 3507:Tooltip Vesicular glutamate transporters 3175:Valproate semisodium (divalproex sodium) 3086:Tooltip γ-Aminobutyrate aminotransferase 2822: 987: 589:. V-ATPase can also be found within the 503:subunits c and c" to become protonated. 349:Bafilomycin A1 specifically targets the 1061: 170: 1609:Shacka JJ, Klocke BJ, Roth KA (2006). 183: 3544:Amido black 10B (naphthol blue black) 2552:Antimicrobial Agents and Chemotherapy 1709:Huss M, Wieczorek H (February 2009). 130: 7: 2179:Cancer Chemotherapy and Pharmacology 840:effect on cancer cell cytotoxicity. 2863:Deramciclane (EGIS-3886, EGYT-3886) 2086:Toxicology and Applied Pharmacology 1865:The Journal of Biological Chemistry 1816:The Journal of Biological Chemistry 1715:The Journal of Experimental Biology 1557:The Journal of Biological Chemistry 1255:The Journal of Biological Chemistry 1211:The Journal of Biological Chemistry 1091:The Journal of Experimental Biology 205: 3722:Tooltip Aspartate aminotransferase 752:, bafilomycin was found to induce 573:V-ATPase localization and function 25: 507:(ATP) is then hydrolyzed by the V 3769:Tooltip Alanine aminotransferase 2033:International Review of Cytology 1389:Toxicology and Industrial Health 521:Bafilomycin–V-ATPase interaction 282: 35: 3915:Tooltip Glutamate decarboxylase 3809:Tooltip Glutamate dehydrogenase 3032:Tooltip Glutamate decarboxylase 2407:10.1016/j.antiviral.2022.105484 2355:Current Opinion in Microbiology 2283:10.1016/j.pneurobio.2017.03.006 278:(at 25 °C , 100 kPa). 3900:Phosphinothricin (glufosinate) 1767:Trends in Biochemical Sciences 933:and decreased their survival. 1: 3960:Receptor/signaling modulators 3250:Receptor/signaling modulators 2367:10.1016/S1369-5274(00)00102-8 2045:10.1016/S0074-7696(03)01005-2 1052:in anti-cancer applications. 965:Some cationic drugs, such as 609:vesicular/protein trafficking 3877:Tooltip Glutamine synthetase 3268:receptor positive modulators 2660:10.1016/j.autrev.2017.05.015 1016:alpha-adrenoreceptor agonist 487:V-ATPase mechanism of action 475:domains of the enzyme. The V 2795:Tooltip γ-Aminobutyric acid 1069:Bafilomycin A1 product page 556:change amino acids in the V 324:produced from a variety of 4048: 2698:10.1016/j.phrs.2016.12.021 2515:10.1007/s11356-021-16427-4 2457:10.1186/s12985-023-01971-x 2318:Molecular Medicine Reports 2156:10.1016/j.phrs.2014.03.005 2106:10.1016/j.taap.2011.12.004 1991:10.1021/acschembio.1c00894 1934:10.1038/s41467-021-22111-5 1779:10.1016/j.tibs.2015.08.005 1659:The Journal of Antibiotics 942:Neurodegenerative diseases 917:The inflammatory myopathy 260:622.83 g/mol 3953: 3603:Glutamic acid (glutamate) 3569:Aspartic acid (aspartate) 3424:-CCG-III ((2S,3S,4R)-CCG) 3381:Glutamic acid (glutamate) 3363:Aspartic acid (aspartate) 3241: 3097:3-Hydrazinopropionic acid 2741:10.1016/j.lfs.2017.08.029 2191:10.1007/s00280-014-2637-z 782:oxidative phosphorylation 272: 225: 94: 48: 43: 34: 3923:3-Mercaptopropionic acid 3432:-Serine-O-sulphate (SOS) 3257:GABA receptor modulators 3043:3-Mercaptopropionic acid 2827:Tooltip GABA transporter 2686:Pharmacological Research 2271:Progress in Neurobiology 2144:Pharmacological Research 1409:10.1177/0748233709103405 1351:. Totowa, N.J.: Humana. 901:, the virus that causes 758:electrochemical gradient 643:Plasma membrane function 532:clathrin coated vesicles 3730:2-Amino-3-butenoic acid 3524:6-(4'-Phenylstyryl)-QDC 3408:-3-Hydroxyaspartic acid 1570:10.1074/jbc.M116.751255 1465:10.1073/pnas.85.21.7972 1010:. The lipophilic agent 919:Inclusion Body Myositis 855:Cryptococcus neoformans 811:reactive oxygen species 776:Bafilomycin acts as an 730:fluorescence microscopy 688:Inhibition of autophagy 351:vacuolar-type H -ATPase 346:damage and cell death. 3895:Methionine sulfoximine 3482:-3-Methylglutamic acid 1878:10.1074/jbc.M605532200 1829:10.1074/jbc.M404638200 1268:10.1074/jbc.M507727200 1224:10.1074/jbc.M003323200 1041:Matrix Metalloprotease 994: 744:Induction of apoptosis 716: 601:Intracellular function 561:bound to bafilomycin. 505:Adenosine triphosphate 465:Adenosine triphosphate 460: 443: 393:Caenorhabditis elegans 2331:10.3892/mmr.2014.2281 1914:Nature Communications 991: 877:Plasmodium falciparum 788:Research applications 710: 454: 441: 372:Discovery and history 322:macrolide antibiotics 3749:-Methylene-aspartate 2648:Autoimmunity Reviews 2564:10.1128/aac.00439-22 1979:ACS Chemical Biology 1553:"Streptomyces lohii" 961:Lysosomotropic drugs 862:in conjunction with 850:ATP-binding cassette 674:follicular lymphomas 379:Streptomyces griseus 4027:Isopropyl compounds 3862:Pyridoxal phosphate 3564:Chicago sky blue 6B 3529:6-Biphenyl-4-yl-QDC 2964:Chicago sky blue 6B 2838:4-Aminovaleric acid 2507:2022ESPR...2912336E 2098:2012ToxAP.259....1M 1926:2021NatCo..12.1782W 1871:(42): 31885–31893. 1822:(32): 33131–33138. 1671:10.1038/ja.2010.147 1515:10.1021/bi00066a008 1456:1988PNAS...85.7972B 1401:2009ToxIH..25..441S 1103:10.1242/jeb.200.1.1 726:electron microscopy 656:V-ATPase in disease 621:protein degradation 579:trans-golgi network 332:biological activity 31: 4002:Secondary alcohols 3885:2-Aminoadipic acid 3754:Hydrazinosuccinate 2501:(8): 12336–12346. 2395:Antiviral Research 2115:20.500.11794/15930 1728:10.1242/jeb.024067 995: 717: 612:receptor recycling 583:secretory vesicles 547:inhibitor of the V 461: 444: 384:cardiac glycosides 320:s are a family of 305:Infobox references 29: 4017:Conjugated dienes 4007:Tertiary alcohols 3979: 3978: 3949: 3948: 3935: 3669: 3668: 3587: 3584:Erythro-4-methyl- 3518: 3439: 3431: 3423: 3415: 3403: 3284: 3283: 3237: 3236: 3208: 3207: 3170:Valproate pivoxil 3134: 3107:γ-Acetylenic-GABA 3012: 3011: 2614:10.3390/v11060524 2242:10.4161/auto.6845 1628:10.4161/auto.2703 1563:(17): 7095–7104. 1509:(15): 3902–3906. 1450:(21): 7972–7976. 1347:Mayers D (2008). 1171:10.1002/cam4.1594 1031:Chemotherapeutics 956:drug interactions 913:Immunosuppressant 313:Chemical compound 311: 310: 16:(Redirected from 4039: 3933: 3916: 3912: 3878: 3874: 3810: 3806: 3794:Propargylglycine 3788: 3780: 3770: 3766: 3748: 3723: 3719: 3690: 3686: 3680: 3661:Xanthurenic acid 3585: 3554:Benzopurpurin 4B 3516: 3508: 3504: 3437: 3429: 3421: 3413: 3401: 3351: 3347: 3341: 3311: 3304: 3297: 3288: 3217: 3160:Sodium valproate 3132: 3087: 3083: 3055: 3033: 3029: 3023: 2944: 2940: 2828: 2824: 2818: 2796: 2792: 2783: 2776: 2769: 2760: 2753: 2752: 2724: 2718: 2717: 2681: 2672: 2671: 2643: 2637: 2636: 2626: 2616: 2592: 2586: 2585: 2575: 2543: 2537: 2536: 2526: 2486: 2480: 2479: 2469: 2459: 2444:Virology Journal 2435: 2429: 2428: 2418: 2385: 2379: 2378: 2350: 2344: 2343: 2333: 2309: 2303: 2302: 2266: 2255: 2254: 2244: 2220: 2211: 2210: 2174: 2168: 2167: 2139: 2128: 2127: 2117: 2080: 2067: 2066: 2028: 2019: 2018: 1970: 1964: 1963: 1953: 1905: 1899: 1898: 1880: 1856: 1850: 1849: 1831: 1807: 1801: 1800: 1790: 1758: 1741: 1740: 1730: 1706: 1693: 1692: 1682: 1650: 1641: 1640: 1630: 1606: 1593: 1592: 1582: 1572: 1548: 1535: 1534: 1494: 1488: 1487: 1477: 1467: 1435: 1429: 1428: 1384: 1371: 1370: 1344: 1333: 1332: 1322: 1311:10.1002/acn3.419 1290: 1281: 1280: 1270: 1246: 1237: 1236: 1226: 1202: 1193: 1192: 1182: 1165:(8): 3800–3811. 1150: 1115: 1114: 1086: 1075: 1066: 985:cultured cells. 793:Anti-tumorigenic 662:male infertility 650:Protein Kinase A 421:Streptomyces sp. 295: 289: 286: 285: 233:Chemical formula 218: 207: 196: 185: 174: 154: 134: 114: 39: 32: 21: 4047: 4046: 4042: 4041: 4040: 4038: 4037: 4036: 3982: 3981: 3980: 3975: 3945: 3914: 3904: 3876: 3866: 3847:Hexachlorophene 3808: 3798: 3786: 3778: 3768: 3758: 3746: 3721: 3711: 3688: 3665: 3628:Reactive blue 2 3506: 3496: 3349: 3330: 3315: 3285: 3280: 3267: 3233: 3204: 3150:Rosmarinic acid 3085: 3075: 3053: 3031: 3008: 2942: 2932: 2826: 2807: 2794: 2787: 2757: 2756: 2726: 2725: 2721: 2683: 2682: 2675: 2645: 2644: 2640: 2594: 2593: 2589: 2558:(7): e0043922. 2545: 2544: 2540: 2488: 2487: 2483: 2437: 2436: 2432: 2387: 2386: 2382: 2352: 2351: 2347: 2311: 2310: 2306: 2268: 2267: 2258: 2222: 2221: 2214: 2176: 2175: 2171: 2141: 2140: 2131: 2082: 2081: 2070: 2055: 2030: 2029: 2022: 1972: 1971: 1967: 1907: 1906: 1902: 1858: 1857: 1853: 1809: 1808: 1804: 1773:(10): 611–622. 1760: 1759: 1744: 1721:(Pt 3): 341–6. 1708: 1707: 1696: 1652: 1651: 1644: 1608: 1607: 1596: 1550: 1549: 1538: 1496: 1495: 1491: 1437: 1436: 1432: 1386: 1385: 1374: 1359: 1346: 1345: 1336: 1292: 1291: 1284: 1261:(44): 36841–7. 1248: 1247: 1240: 1217:(44): 34353–8. 1204: 1203: 1196: 1159:Cancer Medicine 1152: 1151: 1118: 1088: 1087: 1078: 1067: 1063: 1058: 1050:EGFR inhibitors 1033: 1024: 963: 958: 939: 915: 895: 882:red blood cells 872: 846: 795: 790: 774: 746: 690: 682: 680:Cellular action 670:drug resistance 658: 645: 603: 591:plasma membrane 575: 567: 559: 554: 550: 545: 541: 537: 529: 523: 510: 502: 494: 489: 482: 478: 474: 471:and cytosolic V 470: 449: 425:Streptomyces sp 389: 374: 314: 307: 302: 301: 300: ?) 291: 287: 283: 279: 249: 245: 241: 235: 221: 208: 177: 157: 137: 117: 104: 90: 30:Bafilomycin A1 23: 22: 15: 12: 11: 5: 4045: 4043: 4035: 4034: 4029: 4024: 4019: 4014: 4009: 4004: 3999: 3994: 3984: 3983: 3977: 3976: 3954: 3951: 3950: 3947: 3946: 3944: 3943: 3938: 3930: 3925: 3919: 3917: 3906: 3905: 3903: 3902: 3897: 3892: 3887: 3881: 3879: 3868: 3867: 3865: 3864: 3859: 3854: 3849: 3844: 3839: 3834: 3829: 3824: 3819: 3813: 3811: 3800: 3799: 3797: 3796: 3791: 3783: 3773: 3771: 3760: 3759: 3757: 3756: 3751: 3742: 3737: 3732: 3726: 3724: 3713: 3712: 3710: 3709: 3704: 3699: 3693: 3691: 3677: 3671: 3670: 3667: 3666: 3664: 3663: 3658: 3653: 3648: 3640: 3635: 3630: 3625: 3620: 3615: 3610: 3608:Kynurenic acid 3605: 3600: 3595: 3590: 3588:-glutamic acid 3581: 3579:Direct blue 71 3576: 3571: 3566: 3561: 3556: 3551: 3549:Bafilomycin A1 3546: 3541: 3536: 3531: 3526: 3521: 3511: 3509: 3498: 3497: 3495: 3494: 3489: 3484: 3476: 3471: 3466: 3461: 3456: 3451: 3446: 3434: 3426: 3418: 3410: 3398: 3393: 3388: 3383: 3378: 3373: 3365: 3360: 3354: 3352: 3338: 3332: 3331: 3316: 3314: 3313: 3306: 3299: 3291: 3282: 3281: 3279: 3278: 3271: 3265: 3260: 3253: 3246: 3242: 3239: 3238: 3235: 3234: 3232: 3231: 3225: 3223: 3221:Antivitamin B6 3214: 3210: 3209: 3206: 3205: 3203: 3202: 3193: 3192: 3187: 3182: 3177: 3172: 3167: 3162: 3157: 3147: 3142: 3137: 3129: 3124: 3119: 3114: 3109: 3104: 3099: 3090: 3088: 3077: 3076: 3074: 3073: 3064: 3063: 3058: 3050: 3045: 3036: 3034: 3020: 3014: 3013: 3010: 3009: 3007: 3006: 3001: 2996: 2994:Nipecotic acid 2991: 2986: 2984:N-Butyric acid 2981: 2976: 2971: 2966: 2961: 2959:Bafilomycin A1 2956: 2947: 2945: 2934: 2933: 2931: 2930: 2925: 2920: 2915: 2910: 2905: 2900: 2895: 2893:Nipecotic acid 2890: 2885: 2880: 2875: 2870: 2865: 2860: 2855: 2850: 2845: 2840: 2831: 2829: 2815: 2809: 2808: 2788: 2786: 2785: 2778: 2771: 2763: 2755: 2754: 2719: 2673: 2654:(8): 856–874. 2638: 2587: 2538: 2481: 2430: 2380: 2345: 2304: 2256: 2212: 2169: 2129: 2068: 2053: 2020: 1985:(3): 619–628. 1965: 1900: 1851: 1802: 1742: 1694: 1642: 1594: 1536: 1489: 1430: 1372: 1357: 1334: 1305:(6): 422–445. 1282: 1238: 1194: 1116: 1076: 1060: 1059: 1057: 1054: 1039:in decreasing 1032: 1029: 1023: 1020: 1012:xylometazoline 962: 959: 957: 951: 938: 935: 914: 911: 894: 891: 871: 870:Anti-parasitic 868: 845: 842: 794: 791: 789: 786: 773: 770: 745: 742: 698:autophagosomes 689: 686: 681: 678: 657: 654: 644: 641: 632: 631: 629:cell signaling 626: 623: 618: 613: 610: 602: 599: 574: 571: 565: 557: 552: 548: 543: 539: 535: 527: 522: 519: 508: 500: 492: 488: 485: 480: 476: 472: 468: 448: 445: 433:chiral centers 410:concanavalin-A 387: 373: 370: 359:P-type ATPases 327:Streptomycetes 312: 309: 308: 303: 281: 280: 276:standard state 273: 270: 269: 268:Yellow powder 266: 262: 261: 258: 252: 251: 247: 243: 239: 236: 231: 228: 227: 223: 222: 220: 219: 211: 209: 201: 198: 197: 187: 179: 178: 176: 175: 167: 165: 159: 158: 156: 155: 147: 145: 139: 138: 136: 135: 127: 125: 119: 118: 116: 115: 107: 105: 100: 97: 96: 92: 91: 52: 46: 45: 41: 40: 24: 18:Bafilomycin A1 14: 13: 10: 9: 6: 4: 3: 2: 4044: 4033: 4030: 4028: 4025: 4023: 4020: 4018: 4015: 4013: 4010: 4008: 4005: 4003: 4000: 3998: 3995: 3993: 3990: 3989: 3987: 3974: 3973: 3969: 3965: 3961: 3958: 3952: 3942: 3941:Semicarbazide 3939: 3937: 3936:-Allylglycine 3931: 3929: 3926: 3924: 3921: 3920: 3918: 3913: 3907: 3901: 3898: 3896: 3893: 3891: 3888: 3886: 3883: 3882: 3880: 3875: 3869: 3863: 3860: 3858: 3857:Palmitoyl-CoA 3855: 3853: 3852:Hydroxylamine 3850: 3848: 3845: 3843: 3840: 3838: 3835: 3833: 3830: 3828: 3825: 3823: 3820: 3818: 3815: 3814: 3812: 3807: 3801: 3795: 3792: 3790: 3784: 3782: 3775: 3774: 3772: 3767: 3761: 3755: 3752: 3750: 3743: 3741: 3738: 3736: 3733: 3731: 3728: 3727: 3725: 3720: 3714: 3708: 3705: 3703: 3700: 3698: 3695: 3694: 3692: 3687: 3681: 3678: 3676: 3672: 3662: 3659: 3657: 3654: 3652: 3649: 3647: 3645: 3641: 3639: 3636: 3634: 3631: 3629: 3626: 3624: 3621: 3619: 3616: 3614: 3611: 3609: 3606: 3604: 3601: 3599: 3596: 3594: 3591: 3589: 3582: 3580: 3577: 3575: 3572: 3570: 3567: 3565: 3562: 3560: 3557: 3555: 3552: 3550: 3547: 3545: 3542: 3540: 3537: 3535: 3532: 3530: 3527: 3525: 3522: 3520: 3513: 3512: 3510: 3505: 3499: 3493: 3490: 3488: 3485: 3483: 3481: 3477: 3475: 3472: 3470: 3467: 3465: 3462: 3460: 3457: 3455: 3454:Maslinic acid 3452: 3450: 3447: 3445: 3443: 3435: 3433: 3427: 3425: 3419: 3417: 3411: 3409: 3407: 3399: 3397: 3394: 3392: 3389: 3387: 3384: 3382: 3379: 3377: 3374: 3372: 3370: 3366: 3364: 3361: 3359: 3356: 3355: 3353: 3348: 3342: 3339: 3337: 3333: 3329: 3326: 3322: 3319: 3312: 3307: 3305: 3300: 3298: 3293: 3292: 3289: 3277: 3276: 3272: 3270: 3269: 3261: 3259: 3258: 3254: 3252: 3251: 3247: 3244: 3243: 3240: 3230: 3227: 3226: 3224: 3222: 3218: 3215: 3211: 3201: 3200:3-Methyl-GABA 3198: 3195: 3194: 3191: 3188: 3186: 3183: 3181: 3180:Valproic acid 3178: 3176: 3173: 3171: 3168: 3166: 3163: 3161: 3158: 3155: 3151: 3148: 3146: 3143: 3141: 3138: 3136: 3130: 3128: 3125: 3123: 3120: 3118: 3115: 3113: 3110: 3108: 3105: 3103: 3100: 3098: 3095: 3092: 3091: 3089: 3084: 3078: 3072: 3071:3-Methyl-GABA 3069: 3066: 3065: 3062: 3061:Semicarbazide 3059: 3057: 3056:-Allylglycine 3051: 3049: 3046: 3044: 3041: 3038: 3037: 3035: 3030: 3024: 3021: 3019: 3015: 3005: 3002: 3000: 2997: 2995: 2992: 2990: 2987: 2985: 2982: 2980: 2977: 2975: 2972: 2970: 2967: 2965: 2962: 2960: 2957: 2955: 2952: 2949: 2948: 2946: 2941: 2935: 2929: 2926: 2924: 2921: 2919: 2916: 2914: 2911: 2909: 2906: 2904: 2901: 2899: 2896: 2894: 2891: 2889: 2886: 2884: 2883:Ibotenic acid 2881: 2879: 2876: 2874: 2871: 2869: 2866: 2864: 2861: 2859: 2856: 2854: 2851: 2849: 2846: 2844: 2841: 2839: 2836: 2833: 2832: 2830: 2825: 2819: 2816: 2814: 2810: 2806: 2803: 2799: 2793: 2784: 2779: 2777: 2772: 2770: 2765: 2764: 2761: 2750: 2746: 2742: 2738: 2734: 2730: 2729:Life Sciences 2723: 2720: 2715: 2711: 2707: 2703: 2699: 2695: 2691: 2687: 2680: 2678: 2674: 2669: 2665: 2661: 2657: 2653: 2649: 2642: 2639: 2634: 2630: 2625: 2620: 2615: 2610: 2606: 2602: 2598: 2591: 2588: 2583: 2579: 2574: 2569: 2565: 2561: 2557: 2553: 2549: 2542: 2539: 2534: 2530: 2525: 2520: 2516: 2512: 2508: 2504: 2500: 2496: 2492: 2485: 2482: 2477: 2473: 2468: 2463: 2458: 2453: 2449: 2445: 2441: 2434: 2431: 2426: 2422: 2417: 2412: 2408: 2404: 2400: 2396: 2392: 2384: 2381: 2376: 2372: 2368: 2364: 2361:(4): 349–53. 2360: 2356: 2349: 2346: 2341: 2337: 2332: 2327: 2324:(2): 1103–7. 2323: 2319: 2315: 2308: 2305: 2300: 2296: 2292: 2288: 2284: 2280: 2276: 2272: 2265: 2263: 2261: 2257: 2252: 2248: 2243: 2238: 2235:(7): 849–50. 2234: 2230: 2226: 2219: 2217: 2213: 2208: 2204: 2200: 2196: 2192: 2188: 2185:(3): 439–47. 2184: 2180: 2173: 2170: 2165: 2161: 2157: 2153: 2149: 2145: 2138: 2136: 2134: 2130: 2125: 2121: 2116: 2111: 2107: 2103: 2099: 2095: 2091: 2087: 2079: 2077: 2075: 2073: 2069: 2064: 2060: 2056: 2054:9780123646309 2050: 2046: 2042: 2038: 2034: 2027: 2025: 2021: 2016: 2012: 2008: 2004: 2000: 1996: 1992: 1988: 1984: 1980: 1976: 1969: 1966: 1961: 1957: 1952: 1947: 1943: 1939: 1935: 1931: 1927: 1923: 1919: 1915: 1911: 1904: 1901: 1896: 1892: 1888: 1884: 1879: 1874: 1870: 1866: 1862: 1855: 1852: 1847: 1843: 1839: 1835: 1830: 1825: 1821: 1817: 1813: 1806: 1803: 1798: 1794: 1789: 1784: 1780: 1776: 1772: 1768: 1764: 1757: 1755: 1753: 1751: 1749: 1747: 1743: 1738: 1734: 1729: 1724: 1720: 1716: 1712: 1705: 1703: 1701: 1699: 1695: 1690: 1686: 1681: 1676: 1672: 1668: 1665:(1): 159–62. 1664: 1660: 1656: 1649: 1647: 1643: 1638: 1634: 1629: 1624: 1621:(3): 228–30. 1620: 1616: 1612: 1605: 1603: 1601: 1599: 1595: 1590: 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943: 936: 934: 932: 927: 922: 920: 912: 910: 908: 904: 900: 892: 890: 887: 886:P. falciparum 883: 879: 878: 869: 867: 865: 861: 860:C. neoformans 857: 856: 851: 843: 841: 839: 835: 829: 827: 823: 819: 815: 812: 806: 804: 800: 792: 787: 785: 783: 779: 771: 769: 767: 763: 759: 755: 751: 743: 741: 739: 734: 731: 727: 721: 714: 709: 705: 703: 699: 695: 687: 685: 679: 677: 675: 671: 667: 666:osteopetrosis 663: 655: 653: 651: 642: 640: 638: 630: 627: 624: 622: 619: 617: 614: 611: 608: 607: 606: 600: 598: 596: 592: 588: 584: 580: 572: 570: 562: 533: 520: 518: 515: 506: 498: 497:glutamic acid 486: 484: 466: 458: 453: 446: 440: 436: 434: 428: 426: 422: 418: 413: 411: 407: 403: 399: 395: 394: 385: 381: 380: 371: 369: 367: 362: 360: 356: 352: 347: 345: 344:mitochondrial 341: 337: 333: 329: 328: 323: 319: 306: 299: 294: 277: 271: 267: 264: 263: 259: 257: 254: 253: 237: 234: 230: 229: 224: 217: 213: 212: 210: 204: 200: 199: 195: 191: 188: 186: 184:ECHA InfoCard 181: 180: 173: 169: 168: 166: 164: 161: 160: 153: 149: 148: 146: 144: 141: 140: 133: 129: 128: 126: 124: 121: 120: 113: 109: 108: 106: 103: 99: 98: 93: 88: 84: 80: 76: 72: 68: 64: 60: 56: 51: 47: 42: 38: 33: 27: 19: 3956: 3955: 3789:-Cycloserine 3643: 3539:Acid red 114 3515:4-Methylene- 3479: 3441: 3405: 3368: 3273: 3262: 3255: 3248: 3196: 3165:Valnoctamide 3135:-Cycloserine 3093: 3067: 3039: 2950: 2834: 2732: 2728: 2722: 2689: 2685: 2651: 2647: 2641: 2604: 2600: 2590: 2555: 2551: 2541: 2498: 2494: 2484: 2447: 2443: 2433: 2398: 2394: 2383: 2358: 2354: 2348: 2321: 2317: 2307: 2274: 2270: 2232: 2228: 2182: 2178: 2172: 2147: 2143: 2089: 2085: 2036: 2032: 1982: 1978: 1968: 1917: 1913: 1903: 1868: 1864: 1854: 1819: 1815: 1805: 1770: 1766: 1718: 1714: 1662: 1658: 1618: 1614: 1560: 1556: 1506: 1503:Biochemistry 1502: 1492: 1447: 1443: 1433: 1395:(7): 441–6. 1392: 1388: 1348: 1302: 1298: 1258: 1254: 1214: 1210: 1162: 1158: 1094: 1090: 1064: 1034: 1025: 1004: 999: 996: 982: 975:ion trapping 964: 953: 947: 940: 931:plasmablasts 923: 916: 896: 885: 875: 873: 859: 853: 847: 830: 817: 816: 807: 802: 796: 775: 766:osteosarcoma 762:cytochrome c 747: 735: 722: 718: 713:autolysosome 691: 683: 659: 646: 633: 604: 576: 563: 524: 490: 462: 456: 429: 424: 420: 416: 414: 405: 402:synaptosomes 391: 377: 375: 365: 363: 348: 325: 317: 315: 132:ChEMBL290814 95:Identifiers 86: 82: 78: 74: 70: 66: 62: 58: 54: 26: 3992:Antibiotics 3827:Chloroquine 3656:Valinomycin 3651:Trypan blue 3633:Rose bengal 3618:NPPB (N144) 3492:WAY-213,613 3396:Kainic acid 3358:Amphetamine 3336:Transporter 3229:Ginkgotoxin 3197:Activators: 3094:Inhibitors: 3068:Activators: 3040:Inhibitors: 2999:Valinomycin 2951:Inhibitors: 2898:NNC 05-2090 2835:Inhibitors: 2813:Transporter 2692:: 177–184. 2092:(1): 1–12. 2039:: 259–319. 1920:(1): 1782. 1022:Chloroquine 967:chloroquine 864:calcineurin 844:Anti-fungal 838:synergistic 772:K transport 616:endocytosis 595:osteoclasts 457:Attribution 400:) from rat 318:bafilomycin 265:Appearance 226:Properties 190:100.150.187 4022:Macrolides 3986:Categories 3890:JFD01307SC 3623:Ponceau SS 3598:Furosemide 3593:Evans blue 3559:Bumetamide 3519:-glutamate 3328:modulators 3321:metabolism 3190:Vigabatrin 3185:Valpromide 3154:lemon balm 3140:Phenelzine 3122:Gabaculine 3004:Vigabatrin 2969:Evans blue 2913:SKF-89976A 2873:Gabaculine 2848:Arecaidine 2805:modulators 2798:metabolism 2607:(6): 524. 2401:: 105484. 1056:References 971:sertraline 907:Zika virus 899:SARS-CoV-2 893:Anti-viral 799:metastasis 750:PC12 cells 702:cathepsins 417:S. griseus 406:S. griseus 340:ionophores 256:Molar mass 143:ChemSpider 112:88899-55-2 102:CAS Number 50:IUPAC name 3957:See also: 3822:Bithionol 3777:β-Chloro- 3613:Nigericin 3325:transport 3318:Glutamate 3127:Isoniazid 2989:Nigericin 2954:β-Alanine 2928:Tiagabine 2918:SNAP-5114 2843:β-Alanine 2802:transport 2735:: 53–67. 2714:207368923 2450:(1): 18. 2277:: 64–85. 2229:Autophagy 2015:246775779 1999:1554-8937 1942:2041-1723 1887:0021-9258 1838:0021-9258 1615:Autophagy 1523:0006-2960 1367:437345683 1073:Fermentek 1045:cisplatin 993:lysosome. 834:cisplatin 826:sorafenib 822:xenograft 778:ionophore 754:apoptosis 694:Autophagy 625:autophagy 587:endosomes 336:autophagy 4012:Lactones 3781:-alanine 3487:UCPH-101 3474:Theanine 3469:TFB-TBOA 3459:SYM-2081 3444:-2,4-PDC 3245:See also 2908:Riluzole 2888:Muscimol 2878:Guvacine 2749:28866100 2706:28025106 2668:28572049 2633:31174294 2582:35703551 2533:34562220 2476:36721152 2425:36503013 2375:10972492 2340:24890793 2291:28385648 2251:18758232 2207:24642257 2199:25422156 2164:24657238 2124:22198553 2063:12921239 2007:35148071 1960:33741963 1895:16912037 1846:15180988 1797:26410601 1737:19151208 1689:21102599 1637:16874105 1589:28292933 1425:30966042 1417:19736254 1329:28589170 1277:16135514 1233:10915784 1189:29926527 1000:in vitro 983:in vitro 981:seen in 954:In vitro 903:COVID-19 803:in vitro 514:arginine 366:in vitro 355:lysosome 163:DrugBank 152:10251049 3997:Polyols 2979:Glycine 2868:EF-1502 2624:6630673 2601:Viruses 2573:9295568 2524:8475441 2503:Bibcode 2467:9887234 2416:9729583 2299:3811723 2150:: 1–8. 2094:Bibcode 1951:7979754 1922:Bibcode 1788:4589219 1680:5592157 1580:5409476 1531:8385991 1484:2973058 1452:Bibcode 1397:Bibcode 1320:5454400 1180:6089187 1111:9023991 818:In vivo 738:neurons 652:(PKA). 298:what is 296: ( 250: 216:6436223 203:PubChem 172:DB06733 4032:Enones 3842:GW5074 3702:CB-839 3675:Enzyme 3503:vGluTs 3082:GABA-T 3018:Enzyme 2903:NO-711 2853:CI-966 2747: 2712: 2704: 2666: 2631: 2621: 2580: 2570: 2531: 2521: 2474: 2464: 2423: 2413: 2373: 2338: 2297: 2289: 2249: 2205: 2197: 2162: 2122: 2061: 2051: 2013: 2005: 1997: 1958: 1948: 1940: 1893: 1885: 1844: 1836: 1795: 1785: 1735: 1687: 1677: 1635: 1587: 1577: 1529: 1521: 1482: 1475:282335 1472: 1423: 1415: 1365: 1355: 1327: 1317: 1275: 1231: 1187: 1177: 1109: 836:had a 447:Target 293:verify 290: 123:ChEMBL 44:Names 3697:BPTES 3646:-ACDP 3644:trans 3534:7-CKA 3480:threo 3442:trans 3406:threo 3404:-(-)- 3391:HIP-B 3386:HIP-A 3371:-ACBD 3346:EAATs 3213:Other 2939:VIAAT 2710:S2CID 2295:S2CID 2203:S2CID 2011:S2CID 1421:S2CID 1071:from 1037:taxol 1014:, an 1008:aorta 926:Lupus 637:Notch 3928:AAOA 3832:EGCG 3817:AAOA 3735:AAOA 3638:SITS 3574:DIDS 3464:TBOA 3449:MPDC 3416:-αAA 3376:DHKA 3323:and 3264:GABA 3112:AOAA 3102:DABA 3048:AAOA 2974:GABA 2923:TACA 2858:DABA 2800:and 2791:GABA 2745:PMID 2702:PMID 2664:PMID 2629:PMID 2578:PMID 2529:PMID 2472:PMID 2421:PMID 2371:PMID 2336:PMID 2287:PMID 2247:PMID 2195:PMID 2160:PMID 2120:PMID 2059:PMID 2049:ISBN 2003:PMID 1995:ISSN 1956:PMID 1938:ISSN 1891:PMID 1883:ISSN 1842:PMID 1834:ISSN 1793:PMID 1733:PMID 1685:PMID 1633:PMID 1585:PMID 1527:PMID 1519:ISSN 1480:PMID 1413:PMID 1363:OCLC 1353:ISBN 1325:PMID 1273:PMID 1229:PMID 1185:PMID 1107:PMID 969:and 585:and 398:GABA 316:The 3911:GAD 3837:GTP 3805:GDH 3765:ALT 3740:AMB 3718:AST 3707:DON 3685:GAH 3369:cis 3145:PEH 3117:EOS 3028:GAD 2823:GAT 2737:doi 2733:188 2694:doi 2690:117 2656:doi 2619:PMC 2609:doi 2568:PMC 2560:doi 2519:PMC 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