Cyclooxygenase-2 inhibitor - Knowledge (XXG)

2196: (United States Court of Appeals for the Federal Circuit 13 February 2004) ("The University of Rochester ("Rochester") appeals from the decision of the United States District Court for the Western District of New York granting summary judgment that United States Patent 6,048,850 is invalid. Univ. of Rochester v. G.D. Searle & Co., 249 F. Supp. 2d 216 (W.D.N.Y. 2003). Because we conclude that the court did not err in holding the '850 patent invalid for failing to comply with the written description requirement of 35 U.S.C. § 112, P 1, and in granting summary judgment on that ground, we affirm."), archived from 683:. The mechanism for this neuroblastoma HDM2 hyperactivity is unknown. Studies have shown that COX-2 inhibitors block the phosphorylation of HDM2 preventing its activation. In vitro, the use of COX-2 inhibitors lowers the level of active HDM2 found in neuroblastoma cells. The exact process of how COX-2 inhibitors block HDM2 phosphorylation is unknown, but this mediated reduction in active HDM2 concentration level restores the cellular p53 levels. After treatment with a COX-2 inhibitor, the restored p53 function allows DNA damaged neuroblastoma cells to commit suicide through apoptosis reducing the size of growth of the tumor. 574:(FDA) sent a warning letter to the CEO of Merck, stating, "Your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator nonsteroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)." This led to the introduction, in April 2002, of warnings on Vioxx labeling concerning the increased risk of cardiovascular events (heart attack and stroke). By 2005 27: 4070: 4090: 657:(PGA2) and A1 (PGA1), when present in high quantities, bind to p53 in the cytosol and inhibit its ability to cross into the nucleus. This essentially sequesters p53 in the cytosol and prevents apoptosis. Coxibs such as Celebrex (celecoxib), by selectively inhibiting the overexpressed COX-2, allow p53 to work properly. Functional p53 allows DNA damaged neuroblastoma cells to commit 4080: 516:(98.23% of NSAIDs and 94.61% of COX-2 inhibitors were prescribed by primary care physicians). For specialty physicians, rofecoxib and celecoxib were third and fifth most frequently prescribed NSAIDs but first and second in cost, respectively; for primary-care physicians they were ninth and twelfth most frequently prescribed NSAIDs and first and fourth in cost. 270:

additional intracellular components (besides COX-2) were discovered that appear to be important for mediating the anticancer effects of celecoxib in the absence of COX-2. Moreover, a recent study with various malignant tumor cells showed that celecoxib could inhibit the growth of these cells, even though some of these cancer cells didn't even contain COX-2.

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Celebrex (and other brand names for celecoxib) was introduced in 1999 and rapidly became the most frequently prescribed new drug in the United States. By October 2000, its US sales exceeded 100 million prescriptions per year for $ 3 billion, and was still rising. Sales of Celebrex alone reached $ 3.1

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Bombardier and his research team claimed that there was "an increase in myocardial infarction in the patients given rofecoxib (0.4%) compared with those given naproxen (0.1%)" and "patients given naproxen experienced 121 side effects compared with 56 in the patients taking rofecoxib," a "marvellous

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and rofecoxib were about 300 times more potent at inhibiting COX-2 than COX-1, but too toxic for the heart, suggesting the possibility of relief from pain and inflammation without gastrointestinal irritation, and promising to be a boon for those who had previously experienced adverse effects or had

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The VIGOR (Vioxx Gastrointestinal Outcomes Research) trial, "which was the making of Merck's drug rofecoxib (Vioxx)," was at the center of a dispute about the ethics of medical journals. In the VIGOR trial, over 8,000 patients were randomized to receive either naproxen or rofecoxib (Vioxx). Both

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study found that between January 2000 and June 2001, 7% of NSAID prescriptions and 29% of NSAID expenditures were for COX-2 inhibitors. Over the period of the study, COX-2 inhibitors rose from 10.03% of total NSAIDs prescribed by specialty physicians to 29.79%, and from 1.52% to 10.78% of NSAIDs

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function of the selective COX-2 inhibitor celecoxib. However, with regard to this drug's promise for the therapy of advanced cancers, it is unclear whether the inhibition of COX-2 plays a dominant role, and this has become a controversial and intensely researched issue. In recent years, several

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Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. (September 2000). "Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term

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was investigated, it turned out that the antitumor potency did not at all depend on whether or not the respective compound could inhibit COX-2, showing that inhibition of COX-2 was not required for the anticancer effects. One of these compounds, 2,5-dimethyl-celecoxib, which entirely lacks the

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result for Merck" which "contributed to huge sales of rofecoxib." Merck's scientists incorrectly interpreted the finding as a protective effect of naproxen, telling the FDA that the difference in heart attacks "is primarily due to" this protective effect. In September 2001, the United States

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Kardosh A, Wang W, Uddin J, Petasis NA, Hofman FM, Chen TC, Schönthal AH (May 2005). "Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on Burkitt's lymphoma in vitro and in vivo".

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found that while some reviews were no longer valid when the Reuben studies were removed, the conclusions in the majority of them remained unchanged. The review found that the key Reuben claims that needed to be re-examined were "the absence of detrimental effects of coxibs on

306:. These results led Merck to voluntarily withdraw (rofecoxib) from the market in September 2004 and to regulatory authorities imposing a boxed warning on the label of celecoxib. Traditional NSAIDs were also found to have cardiovascular risks, leading to similar 368:, 358 F.3d 916 (Fed. Cir. 2004). The court ruled in favor of Searle in 2004, holding in essence that the university had claimed a method requiring, yet provided no written description of, a compound that could inhibit COX-2 and therefore the patent was invalid. 2612: 360:, alleging breach of contract from relations BYU had with the company at the time of Simmons's work. A settlement was reached in April 2012 in which Pfizer agreed to pay $ 450 million. The other litigation is based on United States Pat. No. 6,048,850 owned by 379:

that spared the positive effects, it was discovered that prostaglandins could indeed be separated into two general classes that could loosely be regarded as "good prostaglandins" and "bad prostaglandins", according to the structure of a particular

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After several COX-2–inhibiting drugs were approved for marketing, data from clinical trials revealed that COX-2 inhibitors caused a significant increase in heart attacks and strokes, with some drugs in the class having worse risks than others.

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Pyrko P, Kardosh A, Liu YT, Soriano N, Xiong W, Chow RH, et al. (April 2007). "Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib".

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The cause of the cardiovascular problems became, and remains, a subject of intensive research. As of 2012 results have been converging on the hypothesis that the adverse cardiovascular effects are most likely due to inhibition of COX-2 in

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Johnsen JI, Lindskog M, Ponthan F, Pettersen I, Elfman L, Orrego A, et al. (October 2004). "Cyclooxygenase-2 is expressed in neuroblastoma, and nonsteroidal anti-inflammatory drugs induce apoptosis and inhibit tumor growth in vivo".

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ability to inhibit COX-2, actually turned out to display stronger anticancer activity than celecoxib itself and this anticancer effect could also be verified in highly drug-resistant tumor cells and in various animal tumor models.

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on their labels. Many COX-2–specific inhibitors have been removed from the US market. As of December 2011, only Celebrex (celecoxib) is still available for purchase in the United States. In the European Union, celecoxib,

2623: 751: 253:. These need to be confirmed in human clinical trials. Current studies support an association of disorders such as these with chronic inflammation, which appears to decrease with the use of COX-2 inhibitors. 731:

Non-steroidal anti-inflammatory drugs (NSAIDs) are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs).

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Lau L, Hansford LM, Cheng LS, Hang M, Baruchel S, Kaplan DR, Irwin MS (March 2007). "Cyclooxygenase inhibitors modulate the p53/HDM2 pathway and enhance chemotherapy-induced apoptosis in neuroblastoma".

2861: 364:, which claimed a method to treat pain without causing gastro-intestinal distress by selectively inhibiting COX-2. When the patent issued, the university sued Searle (later Pfizer) in a case called, 273:

Additional support for the idea that other targets besides COX-2 are important for celecoxib's anticancer effects has come from studies with chemically modified versions of celecoxib. Several dozen

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COX-2 appears to be related to cancers and abnormal growths in the intestinal tract. Overexpression of COX-2 produces excess prostaglandins, which have been shown to increase the possibility of

410:) differ in their relative specificities for COX-2 and COX-1; while aspirin and ibuprofen inhibit COX-2 and COX-1 enzymes, other NSAIDs appear to have partial COX-2 specificity, particularly 3062:

Dai C, Stafford RS, Alexander GC (January 2005). "National trends in cyclooxygenase-2 inhibitor use since market release: nonselective diffusion of a selectively cost-effective innovation".

4561: 2650:"Expression of concern: Bombardier et al., "Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis," N Engl J Med 2000;343:1520-8" 344: 534:

studies concluded that COX-2 specific NSAIDs were associated with significantly fewer adverse gastrointestinal effects. In the CLASS trial which compared Celebrex 800 mg/day to

482:, the beneficial long-term outcome after preemptive administration of coxibs including an allegedly decreased incidence of chronic pain after surgery, and the analgesic efficacy of 1587:

Schönthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA (February 2008). "Celecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs".

525:, and the Vioxx Gastrointestinal Outcomes Research (VIGOR). The VIGOR trial was later proven to have been based on faulty data, and Vioxx was eventually withdrawn from the market. 4073: 3142: 2193: 162:(acetaminophen) inhibits COX-2 almost exclusively within the brain and only minimally in the rest of the body, although it is not considered an NSAID, since it has only minor 2142:, Young DA, O'Banion MK, Winn VD, "Method of inhibiting prostaglandin synthesis in a human host", issued 11 April 2000, assigned to University of Rochester. 418:). Aspirin is ≈170-fold more potent in inhibiting COX-1 than COX-2. Studies of meloxicam 7.5 mg per day for 23 days find a level of gastric injury similar to that of a 1848:"Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials" 37: 743: 437:

that could lead to such complications. Celecoxib is approximately 30 times more potent at inhibiting COX-2 than COX-1, with etoricoxib being 106 times more potent.

633:) appear to have abnormal levels of COX-2 expressed. These studies report that overexpression of the COX-2 enzyme has an adverse effect on the tumor suppressor, 7123: 4554: 1315:"COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia" 281:. Some of these analogs retained COX-2 inhibitory activity, whereas many others didn't. However, when the ability of all these compounds to kill tumor cells in 2899: 2189:

University Of Rochester, Plaintiff-Appellant, V. G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., Defendants-Appellees.

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attacks. COX-2 inhibitors appear to work as well as nonselective NSAIDs, such as aspirin. They have not been compared to other treatment options such as

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Chancellor JV, Hunsche E, de Cruz E, Sarasin FP (2001). "Economic evaluation of celecoxib, a new cyclo-oxygenase 2 specific inhibitor, in Switzerland".

422:, and for meloxicam 15 mg per day a level of injury lower than that of other NSAIDs; however, in clinical practice meloxicam can still cause some 237:

COX-2 inhibitors have been found to be effective in suppressing inflammatory neurodegenerative pathways, with beneficial results in animal studies for

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effort capitalized on these publications; Vioxx was the most heavily advertised prescription drug in 2000, and Celebrex the seventh, according to

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The basic research leading to the discovery of COX-2 inhibitors has been the subject of at least two lawsuits. Brigham Young University has sued

1632:"Antitumor properties of dimethyl-celecoxib, a derivative of celecoxib that does not inhibit cyclooxygenase-2: implications for glioma therapy" 1673:"Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non-COX-2 inhibitory analog of celecoxib" 4048: 2010:"TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue" 1177: 3151: 2121: 3729: 3128: 96: 3120: 4460: 4304: 4263: 1494:"COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro" 461:, research which was found in 2009 to have been faked. Reuben pleaded guilty, paid fines, and served six months in jail, and lost his 2991:"The cost-effectiveness of acetaminophen, NSAIDs, and selective COX-2 inhibitors in the treatment of symptomatic knee osteoarthritis" 2860:

Montero Fernández MJ, Rodríguez Alcalá FJ, Valles Fernández N, López de Castro F, Esteban Tudela M, Cordero García B (October 2002).

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for rheumatoid arthritis, specifically that Vioxx reduced the risk of symptomatic ulcers and clinical upper gastrointestinal events (

4412: 4229: 2197: 837: 71: 4083: 403:, while prostaglandins whose synthesis involves the cyclooxygenase-II enzyme, or COX-2, are responsible for inflammation and pain. 2547:"Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group" 2452:"Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group" 1807:"Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association" 1248: 4421: 2103: 5537: 4335: 4119: 598: 495: 49: 2050: 1367:"Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders" 4381: 4288: 222: 4475: 4309: 519:

Sales and marketing efforts were supported by two large trials, the Celecoxib Long-term Arthritis Safety Study (CLASS) in

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van Durme CM, Wechalekar MD, Landewé RB (June 2015). "Nonsteroidal anti-inflammatory drugs for treatment of acute gout".

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for six months, Celebrex was associated with significantly fewer upper gastrointestinal complications (0.44% vs. 1.27%,

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Analysis of clinical trial data revealed that there was a significant increase in the rate of vascular events like

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van Durme CM, Wechalekar MD, Landewé RB, Pardo Pardo J, Cyril S, van der Heijde D, Buchbinder R (December 2021).

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researcher. The mouse COX-2 gene was cloned by UCLA scientist Harvey Herschman, a finding published in 1991.

4584: 4455: 4433: 4399: 4158: 4052: 1138:"The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment" 470: 361: 5642: 6920: 6840: 4416: 4386: 4352: 4325: 4237: 4153: 513: 400: 2622:. Letter to Raymond V Gilmartin (Merck & Co., Inc). U.S. Food and Drug Administration. Archived from 6897: 5353: 4590: 4465: 4032: 4022: 4017: 4007: 2586: 2081: 581:

Claire Bombardier, a University of Toronto rheumatologist, had claimed that the VIGOR trial showed that

295: 1951:"Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing" 1201:"Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer" 6402: 6372: 6203: 1416:

Müller N (January 2010). "COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence".

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growths. The National Cancer Institute has done some studies on COX-2 and cancer. COX-2 can act as an

7036: 6158: 6011: 5481: 5319: 5228: 4002: 3979: 3460: 3332: 1962: 1907: 638: 547: 323: 5408: 5028: 135:(sold under the brand name Vioxx) was taken off the market in 2004 because of these concerns, while 6255: 6235: 5986: 5791: 5741: 4330: 4245: 4056: 4012: 3929: 3490: 3307: 2545:

Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. (November 2000).

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Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. (November 2000).

2306: 1445:"Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy" 1365:

Sethi R, Gómez-Coronado N, Walker AJ, Robertson OD, Agustini B, Berk M, Dodd S (4 September 2019).

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Chow LW, Loo WT, Toi M (October 2005). "Current directions for COX-2 inhibition in breast cancer".

609:) by 57%, and the risk of bleeding from anywhere in the gastrointestinal tract by 62%. An enormous 6561: 6026: 5916: 5911: 5896: 5831: 5781: 5736: 5301: 4089: 1185: 646: 449:

purportedly conducted clinical research on the use of COX-2 inhibitors, often in combination with

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Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, Kaidi A (March 2009).

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Kardosh A, Soriano N, Liu YT, Uddin J, Petasis NA, Hofman FM, et al. (December 2005).

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Cannon CP, Cannon PJ (June 2012). "Physiology. COX-2 inhibitors and cardiovascular risk".

701:"Studies of local anesthetic action on natural spike activity in the aortic nerve of cats" 672: 665: 462: 198: 174:

Some COX-2 inhibitors are used in a single dose to treat pain after surgery. In this role

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Marret E, Elia N, Dahl JB, McQuay HJ, Møiniche S, Moore RA, et al. (December 2009).

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published an editorial accusing the Bombardier et al. of deliberately withholding data.

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Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, Gupta K (December 2007).

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Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA (March 2007).

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enzyme, but only in specific cases. The FDA has approved Celebrex for treatment of

116: 108: 4539: 4104: 3038: 2711: 1726: 1216: 2383: 2366: 2342: 2325: 823: 330:, so its inhibition can lead to excess clot formation and higher blood pressure. 7046: 6948: 6889: 6759: 6744: 6685: 6650: 6628: 6608: 6556: 6541: 6483: 6441: 6367: 6335: 6320: 6153: 6138: 6063: 6001: 5996: 5670: 5343: 5306: 5281: 5276: 5123: 5079: 5038: 5033: 4931: 4867: 4844: 4834: 4753: 4728: 4695: 4661: 4273: 3944: 3924: 3893: 3878: 3769: 3734: 3723: 3533: 3455: 3383: 3372: 3322: 3317: 2989:

Kamath CC, Kremers HM, Vanness DJ, O'Fallon WM, Cabanela RL, Gabriel SE (2003).

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Kritz FL (September 4, 2001). "You and A: Arthritis drugs. Pain and confusion".

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

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Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (June 2006).

1600: 1564: 1547: 775:"Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man" 614: 539: 454: 450: 429: 218: 194: 175: 149: 3091:

Solomon DH, Avorn J (January 2005). "Coxibs, science, and the public trust".

2428: 2326:"Susceptibility to fraud in systematic reviews: lessons from the Reuben case" 2194:

358 F.3d 916; 2004 U.S. App. LEXIS 2458; 69 U.S.P.Q.2D (BNA) 1886 917

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Zhu J, Song X, Lin HP, Young DC, Yan S, Marquez VE, Chen CS (December 2002).

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where it promotes p53 mediated apoptosis. Two of the metabolites of COX-2,

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indicates initially developed first-in-class compound of specific group;

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enzyme, or COX-1, are responsible for maintenance and protection of the

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Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL (April 1991).

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Chuang HC, Kardosh A, Gaffney KJ, Petasis NA, Schönthal AH (May 2008).

676: 658: 642: 419: 303: 6734: 5935: 4205: 3525: 2008:

Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR (July 1991).

381: 357: 299: 139:(sold under the brand name Celebrex) and traditional NSAIDs received 104: 2923:"Will the promise of the COX-2 selective NSAIDs come to fruition?". 953:"Single dose oral etoricoxib for acute postoperative pain in adults" 178:

appears as good as, if not better than, other pain medications, and

2557:(21). New England Journal of Medicine: 1520–8, 2 p following 1528. 2210:

Ahmadi M, Bekeschus S, Weltmann KD, von Woedtke T, Wende K (2022).

1002:"Single dose oral celecoxib for acute postoperative pain in adults" 904:"Single dose oral rofecoxib for acute postoperative pain in adults" 6546: 4490: 855:"Single dose oral etodolac for acute postoperative pain in adults" 582: 508: 415: 407: 100: 2796:

Green GA (2001). "Understanding NSAIDs: from aspirin to COX-2".

190: 112: 4543: 4108: 3124: 634: 20: 2302:"A Medical Madoff: Anesthesiologist Faked Data in 21 Studies" 349:

The COX-2 enzyme was discovered in 1988 by Daniel Simmons, a

2122:"Pfizer Settles B.Y.U. Lawsuit Over Development of Celebrex" 605:(complicated perforations, obstructions and bleeding in the 277:

of celecoxib were generated with small alterations in their

2827:"COX-2 inhibitors: a CLASS act or Just VIGORously promoted" 2620:

Division of Drug Marketing, Advertising, and Communications

679:

that mediates p53 ligation and tagged destruction, through

822:

Page CP, Curtis MJ, Sutter M, Walker M, Hoffman B (1998).

1184:. United States National Cancer Institute. Archived from 853:

Tirunagari SK, Derry S, Moore RA, McQuay HJ (July 2009).

711:(2). Ovid Technologies (Wolters Kluwer Health): 210–213. 558:

events in patients not taking aspirin for cardiovascular

554:= 0.04), with no significant difference in incidence of 345:

Discovery and development of cyclooxygenase 2 inhibitors

225:(FAP). COX-2 inhibitors are currently being studied in 902:

Bulley S, Derry S, Moore RA, McQuay HJ (October 2009).

45: 1054:"Non-steroidal anti-inflammatory drugs for acute gout" 565:

The VIGOR trial results were published in 2000 in the

115:. Targeting selectivity for COX-2 reduces the risk of 2587:"NAME OF DRUG: Rofecoxib (MK-0966) : Memorandum" 2648:

Curfman GD, Morrissey S, Drazen JM (December 2005).

649:

is damaged beyond repair, p53 is transported to the

7021: 6919: 6896: 6877: 6858: 6813: 5951: 5934: 5709: 5480: 5352: 5255: 5180: 5098: 4983: 4906: 4799: 4781: 4677: 4675: 4620: 4618: 4600: 4583: 4517: 4489: 4365: 4272: 4189: 4182: 4146: 3993: 3912: 3830: 3743: 3579: 3524: 3371: 3281: 3171: 601:) by 54%, to 1.4% from 3%, the risk of complicated 406:

The existing nonsteroidal anti-inflammatory drugs (

5958: 5100: 4985: 4908: 4801: 4783: 4602: 318:, which leads to a decrease in the production of 6879: 6860: 6815: 5257: 2104:"Pfizer, BYU settle Celebrex lawsuit for $ 450M" 664:COX-2 up-regulation has also been linked to the 366:University of Rochester v. G.D. Searle & Co. 2498:"Lapses at the new England journal of medicine" 2077:"BYU spices up Celebrex lawsuit against Pfizer" 99:(NSAID) that directly target cyclooxygenase-2 ( 6921: 2931:(11). Adis International Limited: 6–10. 2001. 1199:Desai SJ, Prickril B, Rasooly A (April 2018). 773:Hinz B, Cheremina O, Brune K (February 2008). 699:Lipfert P, Seitz R, Arndt JO (February 1987). 6898: 5354: 4555: 4120: 3136: 2825:Malhotra S, Shafiq N, Pandhi P (March 2004). 2491: 2489: 2487: 261:The inhibition of COX-2 is paramount for the 34:The examples and perspective in this article 8: 5482: 2367:"The Scott Reuben saga: one last retraction" 2365:White PF, Rosow CE, Shafer SL (March 2011). 2051:"University sues Pfizer over COX-2 research" 395:Prostaglandins whose synthesis involves the 189:NSAIDs are often used in treatment of acute 2743: 2741: 2739: 2737: 1058:The Cochrane Database of Systematic Reviews 1006:The Cochrane Database of Systematic Reviews 957:The Cochrane Database of Systematic Reviews 908:The Cochrane Database of Systematic Reviews 859:The Cochrane Database of Systematic Reviews 371:In the course of the search for a specific 16:Type of nonsteroidal anti-inflammatory drug 5948: 4796: 4615: 4597: 4562: 4548: 4540: 4186: 4127: 4113: 4105: 3143: 3129: 3121: 1249:"FDA Approves Celebrex for New Indication" 3006: 2885: 2842: 2665: 2562: 2521: 2467: 2382: 2341: 2319: 2317: 2276: 2235: 2025: 1984: 1974: 1893: 1891: 1871: 1822: 1688: 1647: 1563: 1519: 1509: 1468: 1392: 1382: 1338: 1224: 1153: 1077: 1025: 976: 927: 878: 790: 716: 661:through apoptosis, halting tumor growth. 127:, and other members of this drug class. 72:Learn how and when to remove this message 2502:Journal of the Royal Society of Medicine 1552:Journal of the National Cancer Institute 1418:Current Opinion in Investigational Drugs 951:Clarke R, Derry S, Moore RA (May 2014). 322:in them. Prostacyclin usually prevents 2160:"Reach-Through Claims Declared Invalid" 1589:Expert Opinion on Investigational Drugs 691: 5953: 1800: 1798: 1796: 1541: 1539: 744:"Public data from Article 57 database" 529:VIGOR study and publishing controversy 457:, for the prevention and treatment of 3152:Non-steroidal anti-inflammatory drugs 1360: 1358: 7: 7124:Nonsteroidal anti-inflammatory drugs 6576:Selective COX-2 inhibitors (coxibs): 4079: 1047: 1045: 302:with COX-2 inhibitors compared with 4685:Tooltip Prostaglandin D2 receptor 2 4628:Tooltip Prostaglandin D2 receptor 1 3730:COX-inhibiting nitric oxide donator 2654:The New England Journal of Medicine 2551:The New England Journal of Medicine 2456:The New England Journal of Medicine 2259:Awtry EH, Loscalzo J (March 2000). 2014:The Journal of Biological Chemistry 576:The New England Journal of Medicine 97:nonsteroidal anti-inflammatory drug 6547:AM-404 (N-arachidonoylaminophenol) 6365:Anthranilic acids (fenamic acids): 6017:Mesalazine (5-aminosalicylic acid) 5108:Tooltip Prostaglandin EP4 receptor 4993:Tooltip Prostaglandin EP3 receptor 4916:Tooltip Prostaglandin EP2 receptor 4809:Tooltip Prostaglandin EP1 receptor 2462:(21): 1520–8, 2 p following 1528. 1255:. 23 December 1999. Archived from 1000:Derry S, Moore RA (October 2013). 152:have been approved for use by the 14: 7037:γ-Linolenic acid (gamolenic acid) 6383:Meclofenamic acid (meclofenamate) 4792:Tooltip Prostaglandin E2 receptor 4611:Tooltip Prostaglandin D2 receptor 1824:10.1161/CIRCULATIONAHA.106.181424 1280:Biomedicine & Pharmacotherapy 1253:U.S. Food and Drug Administration 585:50 mg/day had benefits over 182:appears to be about as useful as 7092:Leukotriene signaling modulators 6884:Tooltip Prostaglandin F synthase 6865:Tooltip Prostaglandin E synthase 6824:Tooltip Prostaglandin D synthase 5266:Tooltip Prostaglandin F receptor 4088: 4078: 4069: 4068: 3008:10.1046/j.1524-4733.2003.00215.x 2966:10.2165/00019053-200119001-00005 2937:10.2165/00042310-200117110-00002 2925:Drugs & Therapy Perspectives 718:10.1097/00000542-198702000-00016 25: 7119:Experimental medical treatments 6403:Talinflumic acid (talinflumate) 6393:Morniflumic acid (morniflumate) 6373:Floctafenic acid (floctafenate) 6356:Tiaprofenic acid (tiaprofenate) 3980:Superoxide dismutase / orgotein 2611:Abrams TW (17 September 2001). 2128:. Associated Press. 1 May 2012. 2053:. The Scientist. Archived from 754:from the original on 2018-10-02 567:New England Journal of Medicine 496:intravenous regional anesthesia 6926:Tooltip Thromboxane A synthase 5977:Aspirin (acetylsalicylic acid) 5191:16,16-Dimethyl Prostaglandin E 3292:Aspirin (acetylsalicylic acid) 2164:Publications: Hodgson Russ LLP 1443:Schönthal AH (December 2007). 1070:10.1002/14651858.CD010120.pub3 1018:10.1002/14651858.CD004233.pub4 969:10.1002/14651858.CD004309.pub4 920:10.1002/14651858.CD004604.pub3 871:10.1002/14651858.CD007357.pub2 223:familial adenomatous polyposis 1: 7085:Receptor/signaling modulators 6907:Tooltip Prostacyclin synthase 6408:Tolfenamic acid (tolfenamate) 6378:Flufenamic acid (flufenamate) 6368:Etofenamic acid (etofenamate) 5424:Prostacyclin (prostaglandin I 5363:Tooltip Prostacyclin receptor 3093:Archives of Internal Medicine 3064:Archives of Internal Medicine 3039:10.1158/0008-5472.CAN-04-1795 2878:10.1016/s0212-6567(02)79048-3 2810:10.1016/S1098-3597(01)90069-9 2712:10.1158/0008-5472.CAN-04-1795 2027:10.1016/S0021-9258(18)98774-0 1727:10.1158/1535-7163.MCT-06-0629 1715:Molecular Cancer Therapeutics 1292:10.1016/S0753-3322(05)80046-0 1217:10.1080/01635581.2018.1446091 1178:"COX-2 Inhibitors and Cancer" 603:upper gastrointestinal events 251:obsessive-compulsive disorder 229:and appear to be beneficial. 5491:Tooltip Thromboxane receptor 2384:10.1213/ANE.0b013e318209736f 2343:10.1097/ALN.0b013e3181c14c3d 1759:Cancer Biology & Therapy 607:upper gastrointestinal tract 572:Food and Drug Administration 502:Early COX-2-inhibiting drugs 6557:Paracetamol (acetaminophen) 6388:Mefenamic acid (mefenamate) 6042:Salicylate (salicylic acid) 3358:Salicylic acid (salicylate) 2564:10.1056/NEJM200011233432103 2469:10.1056/NEJM200011233432103 2300:Borrell B (10 March 2009). 1630:Schönthal AH (April 2006). 375:of the negative effects of 119:and is the main feature of 85:Cyclooxygenase-2 inhibitors 48:, discuss the issue on the 7140: 6236:Bucloxic acid (blucloxate) 6154:Indometacin (indomethacin) 4305:Dihydropteroate synthetase 4164:Non-competitive inhibition 3105:10.1001/archinte.165.2.158 3076:10.1001/archinte.165.2.171 2514:10.1177/014107680609900802 2278:10.1161/01.cir.101.10.1206 1690:10.1182/blood-2005-07-2819 627:sympathetic nervous system 342: 233:Neuropsychiatric disorders 7076: 6398:Niflumic acid (niflumate) 5502:Carbocyclic thromboxane A 4525:Steroidogenesis inhibitor 4064: 4041: 2415:Arthritis Safety Study". 1864:10.1136/bmj.332.7553.1302 1601:10.1517/13543784.17.2.197 1449:British Journal of Cancer 1319:British Journal of Cancer 842:– via Google Books. 748:European Medicines Agency 668:and activation of the E3 239:major depressive disorder 154:European Medicines Agency 6716:Menatetrenone (vitamin K 6539:Aminophenols (anilines): 4461:Matrix metalloproteinase 4264:Ribonucleotide reductase 4159:Uncompetitive inhibition 4028:Naproxen/diphenhydramine 2429:10.1001/jama.284.10.1247 2371:Anesthesia and Analgesia 2102:Harvey T (May 1, 2012). 1649:10.3171/foc.2006.20.4.14 1384:10.3389/fpsyt.2019.00605 351:Brigham Young University 7042:Dihomo-γ-linolenic acid 6439:Enolic acids (oxicams): 5982:Benorilate (benorylate) 4230:Dihydrofolate reductase 4049:WHO-Essential Medicines 2496:Smith R (August 2006). 2216:RSC Medicinal Chemistry 2075:Harvey T (2010-09-21). 2049:Yajnik J (2006-10-27). 1920:10.1126/science.1224398 1565:10.1093/jnci/94.23.1745 1371:Frontiers in Psychiatry 637:. p53 is an apoptosis 514:primary care physicians 471:evidence-based medicine 445:Between 1996 and 2009, 362:University of Rochester 6841:selenium tetrachloride 4326:Nucleotidyltransferase 4154:Competitive inhibition 3377:and related substances 2763:10.1038/sj.onc.1209981 1976:10.1073/pnas.88.7.2692 1511:10.1186/1476-4598-7-38 1461:10.1038/sj.bjc.6604049 1331:10.1038/sj.bjc.6604057 1286:(Suppl 2): S281–S284. 1115:10.1001/jama.2015.1881 825:Farmacología integrada 641:normally found in the 401:gastrointestinal tract 6510:Aminonicotinic acids: 4336:Reverse transcriptase 4033:Naproxen/esomeprazole 4023:Meloxicam/bupivacaine 4018:Ibuprofen/paracetamol 4008:Ibuprofen/hydrocodone 2200: on 21 July 2013. 2158:Kadle R, ed. (2010). 2108:The Salt Lake Tribune 2082:The Salt Lake Tribune 1155:10.1093/carcin/bgp014 792:10.1096/fj.07-8506com 750:. 17 September 2018. 538:2400 mg/day and 343:Further information: 296:myocardial infarction 6159:Indometacin farnesil 6012:Magnesium salicylate 5643:Pinane thromboxane A 5404:Iloprost (ciloprost) 5024:Iloprost (ciloprost) 4830:Iloprost (ciloprost) 4382:Acetylcholinesterase 4289:Thymidylate synthase 4003:Ibuprofen/famotidine 3461:Indometacin farnesil 3333:Magnesium salicylate 3154:(NSAIDs) (primarily 2798:Clinical Cornerstone 1771:10.4161/cbt.4.5.1699 1205:Nutrition and Cancer 639:transcription factor 625:Small tumors of the 548:rheumatoid arthritis 542:150 mg/day for 465:. A 2009 review of 324:platelet aggregation 54:create a new article 46:improve this article 36:may not represent a 5987:Carbasalate calcium 4476:Histone deacetylase 4310:Farnesyltransferase 4013:Ibuprofen/oxycodone 3930:Chondroitin sulfate 3308:Carbasalate calcium 2667:10.1056/NEJMe058314 2307:Scientific American 2020:(20): 12866–12872. 1967:1991PNAS...88.2692X 1912:2012Sci...336.1386C 1906:(6087): 1386–1387. 1858:(7553): 1302–1308. 1636:Neurosurgical Focus 507:billion in 2001. A 279:chemical structures 6849:selenium disulfide 6481:4-Aminoquinolines: 4509:Carbonic anhydrase 4501:Dopa decarboxylase 4169:Suicide inhibition 3920:Aminopropionitrile 2960:(Suppl 1): 59–75. 2228:10.1039/D1MD00280E 2126:The New York Times 459:postoperative pain 384:involved in their 7101: 7100: 7017: 7016: 6052:Sodium salicylate 6022:Methyl salicylate 5945: 5930: 5929: 5251: 5250: 4777: 4776: 4594: 4537: 4536: 4533: 4532: 4405:Alpha-glucosidase 4395:Polygalacturonase 4377:Phosphodiesterase 4318:GABA transaminase 4222:Monoamine oxidase 4206:HMG-CoA reductase 4140:enzyme inhibition 4102: 4101: 3950:Glycosaminoglycan 3800:Meclofenamic acid 3363:Sodium salicylate 3338:Methyl salicylate 3033:(20): 7210–7215. 2954:PharmacoEconomics 2866:Atencion Primaria 2757:(13): 1920–1931. 2706:(20): 7210–7215. 2660:(26): 2813–2814. 2629:on 6 January 2012 2423:(10): 1247–1255. 2271:(10): 1206–1218. 1817:(12): 1634–1642. 1683:(13): 4330–4338. 1558:(23): 1745–1757. 1455:(11): 1465–1468. 1325:(11): 1523–1531. 1109:(22): 2276–2277. 492:local anesthetics 263:anti-inflammatory 211:colorectal cancer 164:anti-inflammatory 117:peptic ulceration 91:), also known as 82: 81: 74: 56:, as appropriate. 7131: 7114:COX-2 inhibitors 7052:Arachidonic acid 6927: 6923: 6908: 6904: 6885: 6881: 6866: 6862: 6825: 6821: 6648:Others/unsorted: 6223:Propionic acids: 6204:Sulindac sulfide 5969:Salicylic acids: 5960: 5955: 5949: 5939: 5492: 5488: 5364: 5360: 5267: 5263: 5109: 5105: 4994: 4990: 4917: 4913: 4810: 4806: 4797: 4793: 4789: 4686: 4682: 4629: 4625: 4616: 4612: 4608: 4598: 4588: 4564: 4557: 4550: 4541: 4259:Xanthine oxidase 4201:Aldose reductase 4187: 4174:Mixed inhibition 4129: 4122: 4115: 4106: 4092: 4082: 4081: 4072: 4071: 3832:COX-2 inhibitors 3747:-arylanthranilic 3714:Tiaprofenic acid 3145: 3138: 3131: 3122: 3116: 3087: 3058: 3020: 3010: 2985: 2948: 2919: 2910: 2908: 2907: 2898:. Archived from 2889: 2856: 2846: 2821: 2783: 2782: 2745: 2732: 2731: 2694: 2688: 2687: 2669: 2645: 2639: 2638: 2636: 2634: 2628: 2617: 2613:"Warning Letter" 2608: 2602: 2601: 2599: 2597: 2591: 2583: 2577: 2576: 2566: 2542: 2536: 2535: 2525: 2493: 2482: 2481: 2471: 2447: 2441: 2440: 2411: 2405: 2404: 2386: 2362: 2356: 2355: 2345: 2336:(6): 1279–1289. 2321: 2312: 2311: 2297: 2291: 2290: 2280: 2256: 2250: 2249: 2239: 2207: 2201: 2191: 2185: 2179: 2178: 2176: 2175: 2170:on 1 August 2010 2166:. Archived from 2155: 2149: 2148: 2147: 2143: 2136: 2130: 2129: 2118: 2112: 2111: 2099: 2093: 2092: 2090: 2089: 2072: 2066: 2065: 2063: 2062: 2046: 2040: 2039: 2029: 2005: 1999: 1998: 1988: 1978: 1961:(7): 2692–2696. 1946: 1940: 1939: 1895: 1886: 1885: 1875: 1843: 1837: 1836: 1826: 1802: 1791: 1790: 1753: 1747: 1746: 1721:(4): 1262–1275. 1709: 1703: 1702: 1692: 1668: 1662: 1661: 1651: 1627: 1621: 1620: 1584: 1578: 1577: 1567: 1543: 1534: 1533: 1523: 1513: 1498:Molecular Cancer 1489: 1483: 1482: 1472: 1440: 1434: 1433: 1413: 1407: 1406: 1396: 1386: 1362: 1353: 1352: 1342: 1310: 1304: 1303: 1275: 1269: 1268: 1266: 1264: 1245: 1239: 1238: 1228: 1196: 1190: 1189: 1174: 1168: 1167: 1157: 1133: 1127: 1126: 1098: 1092: 1091: 1081: 1064:(12): CD010120. 1049: 1040: 1039: 1029: 1012:(10): CD004233. 997: 991: 990: 980: 948: 942: 941: 931: 899: 893: 892: 882: 850: 844: 843: 819: 813: 812: 794: 770: 764: 763: 761: 759: 740: 734: 733: 720: 696: 670:ubiquitin ligase 655:prostaglandin A2 397:cyclooxygenase-I 339:Research history 328:vasoconstriction 247:bipolar disorder 107:responsible for 95:, are a type of 89:COX-2 inhibitors 77: 70: 66: 63: 57: 29: 28: 21: 7139: 7138: 7134: 7133: 7132: 7130: 7129: 7128: 7104: 7103: 7102: 7097: 7072: 7068: 7065:Prostaglandin H 7060: 7057:Prostaglandin G 7013: 6925: 6915: 6913:Tranylcypromine 6906: 6902: 6892: 6883: 6873: 6864: 6854: 6845:sodium selenite 6823: 6819: 6809: 6755:Rosmarinic acid 6719: 6527:Sulfonanilides: 6430:Oxyphenbutazone 5956: 5938: 5926: 5705: 5646: 5518: 5505: 5490: 5486: 5476: 5436: 5433:Prostaglandin E 5428:, epoprostenol) 5427: 5362: 5358: 5348: 5323: 5320:Prostaglandin F 5315: 5312:Prostaglandin D 5265: 5261: 5247: 5232: 5229:Prostaglandin F 5194: 5176: 5141: 5138:Prostaglandin E 5132: 5129:Prostaglandin E 5107: 5104: 5094: 5075:Ricinoleic acid 5064: 5061:Prostaglandin E 5055: 5052:Prostaglandin E 5047: 5044:Prostaglandin D 4992: 4989: 4979: 4949: 4946:Prostaglandin E 4940: 4937:Prostaglandin E 4915: 4912: 4902: 4862: 4859:Prostaglandin E 4853: 4850:Prostaglandin E 4808: 4805: 4791: 4787: 4773: 4704: 4701:Prostaglandin D 4684: 4681: 4671: 4642: 4639:Prostaglandin D 4627: 4624: 4610: 4606: 4587: 4579: 4568: 4538: 4529: 4513: 4485: 4361: 4348:Tyrosine kinase 4268: 4178: 4142: 4133: 4103: 4098: 4060: 4053:withdrawn drugs 4037: 3995: 3989: 3908: 3834: 3826: 3822:Tolfenamic acid 3780:Flufenamic acid 3748: 3739: 3583: 3575: 3520: 3376: 3367: 3277: 3246:Oxyphenbutazone 3176: 3167: 3149: 3119: 3090: 3061: 3027:Cancer Research 3023: 2995:Value in Health 2988: 2951: 2922: 2918:. p. HE01. 2916:Washington Post 2913: 2905: 2903: 2859: 2824: 2795: 2791: 2789:Further reading 2786: 2747: 2746: 2735: 2700:Cancer Research 2696: 2695: 2691: 2647: 2646: 2642: 2632: 2630: 2626: 2615: 2610: 2609: 2605: 2595: 2593: 2589: 2585: 2584: 2580: 2544: 2543: 2539: 2495: 2494: 2485: 2449: 2448: 2444: 2413: 2412: 2408: 2364: 2363: 2359: 2323: 2322: 2315: 2299: 2298: 2294: 2258: 2257: 2253: 2209: 2208: 2204: 2187: 2186: 2182: 2173: 2171: 2157: 2156: 2152: 2145: 2138: 2137: 2133: 2120: 2119: 2115: 2101: 2100: 2096: 2087: 2085: 2074: 2073: 2069: 2060: 2058: 2048: 2047: 2043: 2007: 2006: 2002: 1948: 1947: 1943: 1897: 1896: 1889: 1845: 1844: 1840: 1804: 1803: 1794: 1755: 1754: 1750: 1711: 1710: 1706: 1670: 1669: 1665: 1629: 1628: 1624: 1586: 1585: 1581: 1545: 1544: 1537: 1491: 1490: 1486: 1442: 1441: 1437: 1415: 1414: 1410: 1364: 1363: 1356: 1312: 1311: 1307: 1277: 1276: 1272: 1262: 1260: 1259:on May 10, 2008 1247: 1246: 1242: 1198: 1197: 1193: 1188:on May 9, 2008. 1176: 1175: 1171: 1135: 1134: 1130: 1100: 1099: 1095: 1051: 1050: 1043: 999: 998: 994: 963:(5): CD004309. 950: 949: 945: 914:(4): CD004604. 901: 900: 896: 865:(3): CD007357. 852: 851: 847: 840: 821: 820: 816: 772: 771: 767: 757: 755: 742: 741: 737: 698: 697: 693: 689: 666:phosphorylation 623: 531: 504: 463:medical license 443: 426:complications. 347: 341: 336: 292: 290:Adverse effects 259: 235: 207: 199:glucocorticoids 172: 78: 67: 61: 58: 43: 30: 26: 17: 12: 11: 5: 7137: 7135: 7127: 7126: 7121: 7116: 7106: 7105: 7099: 7098: 7096: 7095: 7088: 7081: 7077: 7074: 7073: 7071: 7070: 7066: 7062: 7058: 7054: 7049: 7047:Diacylglycerol 7044: 7039: 7034: 7025: 7023: 7019: 7018: 7015: 7014: 7012: 7011: 7006: 7001: 6996: 6991: 6986: 6981: 6976: 6971: 6966: 6961: 6956: 6951: 6946: 6941: 6936: 6930: 6928: 6917: 6916: 6911: 6909: 6900: 6894: 6893: 6888: 6886: 6875: 6874: 6869: 6867: 6856: 6855: 6853: 6852: 6834: 6828: 6826: 6817: 6811: 6810: 6808: 6807: 6802: 6797: 6792: 6787: 6782: 6777: 6772: 6767: 6762: 6757: 6752: 6747: 6742: 6737: 6732: 6727: 6722: 6717: 6713: 6708: 6703: 6698: 6693: 6688: 6683: 6678: 6673: 6668: 6663: 6658: 6653: 6641: 6636: 6631: 6626: 6621: 6616: 6611: 6606: 6601: 6596: 6591: 6586: 6581: 6569: 6564: 6559: 6554: 6549: 6544: 6532: 6520: 6515: 6503: 6491: 6486: 6474: 6469: 6464: 6459: 6454: 6449: 6444: 6435:Phenylbutazone 6432: 6427: 6422: 6417: 6405: 6400: 6395: 6390: 6385: 6380: 6375: 6370: 6358: 6353: 6348: 6343: 6338: 6333: 6328: 6323: 6318: 6313: 6308: 6303: 6298: 6293: 6288: 6283: 6278: 6273: 6268: 6263: 6258: 6253: 6248: 6243: 6238: 6233: 6228: 6216: 6211: 6206: 6201: 6196: 6191: 6186: 6181: 6176: 6171: 6166: 6161: 6156: 6151: 6146: 6141: 6136: 6131: 6126: 6121: 6116: 6111: 6106: 6101: 6096: 6091: 6086: 6081: 6076: 6071: 6066: 6054: 6049: 6044: 6039: 6034: 6029: 6024: 6019: 6014: 6009: 6004: 5999: 5994: 5989: 5984: 5979: 5974: 5965: 5963: 5946: 5932: 5931: 5928: 5927: 5925: 5924: 5919: 5914: 5909: 5904: 5899: 5894: 5889: 5884: 5879: 5874: 5869: 5864: 5859: 5854: 5849: 5844: 5839: 5834: 5829: 5824: 5819: 5814: 5809: 5804: 5799: 5794: 5789: 5784: 5779: 5774: 5769: 5764: 5759: 5754: 5749: 5744: 5739: 5734: 5729: 5724: 5719: 5713: 5711: 5707: 5706: 5704: 5703: 5698: 5693: 5688: 5683: 5678: 5673: 5668: 5663: 5658: 5653: 5648: 5644: 5640: 5635: 5630: 5625: 5620: 5615: 5610: 5605: 5600: 5595: 5590: 5585: 5580: 5575: 5570: 5565: 5560: 5555: 5550: 5545: 5540: 5531: 5530: 5525: 5520: 5516: 5512: 5507: 5503: 5495: 5493: 5484: 5478: 5477: 5475: 5474: 5465: 5464: 5459: 5454: 5449: 5444: 5439: 5434: 5430: 5425: 5421: 5416: 5411: 5409:Isocarbacyclin 5406: 5401: 5396: 5391: 5386: 5381: 5376: 5367: 5365: 5356: 5350: 5349: 5347: 5346: 5341: 5336: 5331: 5326: 5321: 5317: 5313: 5309: 5304: 5299: 5294: 5289: 5284: 5279: 5270: 5268: 5259: 5253: 5252: 5249: 5248: 5246: 5245: 5240: 5235: 5230: 5226: 5221: 5216: 5211: 5206: 5201: 5196: 5192: 5184: 5182: 5178: 5177: 5175: 5174: 5169: 5164: 5159: 5150: 5149: 5144: 5142:(dinoprostone) 5139: 5135: 5130: 5126: 5121: 5112: 5110: 5102: 5096: 5095: 5093: 5092: 5083: 5082: 5077: 5072: 5067: 5065:(dinoprostone) 5062: 5058: 5053: 5049: 5045: 5041: 5036: 5031: 5029:Isocarbacyclin 5026: 5021: 5016: 5011: 5006: 4997: 4995: 4987: 4981: 4980: 4978: 4977: 4972: 4967: 4958: 4957: 4952: 4950:(dinoprostone) 4947: 4943: 4938: 4934: 4929: 4920: 4918: 4910: 4904: 4903: 4901: 4900: 4895: 4890: 4885: 4880: 4871: 4870: 4865: 4863:(dinoprostone) 4860: 4856: 4851: 4847: 4842: 4837: 4832: 4827: 4822: 4813: 4811: 4803: 4794: 4785: 4779: 4778: 4775: 4774: 4772: 4771: 4766: 4761: 4756: 4751: 4746: 4741: 4736: 4731: 4726: 4721: 4716: 4707: 4706: 4702: 4698: 4689: 4687: 4679: 4673: 4672: 4670: 4669: 4664: 4659: 4650: 4649: 4644: 4640: 4632: 4630: 4622: 4613: 4604: 4595: 4581: 4580: 4569: 4567: 4566: 4559: 4552: 4544: 4535: 4534: 4531: 4530: 4528: 4527: 4521: 4519: 4515: 4514: 4512: 4511: 4504: 4503: 4496: 4494: 4487: 4486: 4484: 4483: 4481:Beta-lactamase 4478: 4471: 4470: 4469: 4468: 4463: 4458: 4448: 4447: 4446: 4441: 4431: 4430: 4429: 4424: 4408: 4407: 4402: 4397: 4390: 4389: 4384: 4379: 4372: 4370: 4363: 4362: 4360: 4359: 4358: 4357: 4356: 4355: 4343:Protein kinase 4340: 4339: 4338: 4333: 4321: 4320: 4313: 4312: 4307: 4300: 4299: 4292: 4291: 4286: 4279: 4277: 4270: 4269: 4267: 4266: 4261: 4254: 4253: 4248: 4241: 4240: 4233: 4232: 4225: 4224: 4217: 4216: 4209: 4208: 4203: 4196: 4194: 4191:Oxidoreductase 4184: 4180: 4179: 4177: 4176: 4171: 4166: 4161: 4156: 4150: 4148: 4144: 4143: 4134: 4132: 4131: 4124: 4117: 4109: 4100: 4099: 4097: 4096: 4086: 4076: 4065: 4062: 4061: 4057:veterinary use 4042: 4039: 4038: 4036: 4035: 4030: 4025: 4020: 4015: 4010: 4005: 3999: 3997: 3991: 3990: 3988: 3987: 3982: 3977: 3972: 3967: 3962: 3957: 3952: 3947: 3942: 3937: 3932: 3927: 3922: 3916: 3914: 3910: 3909: 3907: 3906: 3901: 3896: 3891: 3886: 3881: 3876: 3871: 3866: 3861: 3856: 3844: 3838: 3836: 3828: 3827: 3825: 3824: 3819: 3814: 3809: 3806:Mefenamic acid 3802: 3797: 3792: 3787: 3782: 3777: 3772: 3767: 3762: 3756: 3754: 3741: 3740: 3738: 3737: 3726: 3721: 3716: 3711: 3706: 3701: 3696: 3691: 3686: 3681: 3676: 3669: 3664: 3659: 3654: 3649: 3644: 3637: 3632: 3627: 3622: 3617: 3612: 3607: 3602: 3597: 3591: 3589: 3581:propionic acid 3577: 3576: 3574: 3573: 3568: 3563: 3556: 3551: 3546: 3541: 3536: 3530: 3528: 3522: 3521: 3519: 3518: 3513: 3508: 3503: 3498: 3493: 3488: 3483: 3478: 3473: 3468: 3463: 3458: 3453: 3448: 3446:Fenclozic acid 3443: 3438: 3433: 3428: 3421: 3416: 3411: 3406: 3401: 3396: 3391: 3386: 3380: 3378: 3369: 3368: 3366: 3365: 3360: 3355: 3350: 3345: 3340: 3335: 3330: 3325: 3320: 3315: 3310: 3305: 3300: 3295: 3287: 3285: 3279: 3278: 3276: 3275: 3270: 3268:Sulfinpyrazone 3265: 3263:Propyphenazone 3260: 3257:Phenylbutazone 3253: 3248: 3243: 3238: 3233: 3228: 3223: 3218: 3213: 3208: 3203: 3198: 3193: 3188: 3186:Aminophenazone 3182: 3180: 3169: 3168: 3150: 3148: 3147: 3140: 3133: 3125: 3118: 3117: 3099:(2): 158–160. 3088: 3070:(2): 171–177. 3059: 3021: 3001:(2): 144–157. 2986: 2949: 2920: 2911: 2872:(6): 363–367. 2868:(in Spanish). 2857: 2822: 2792: 2790: 2787: 2785: 2784: 2733: 2689: 2640: 2603: 2578: 2537: 2508:(8): 380–382. 2483: 2442: 2406: 2377:(3): 512–515. 2357: 2330:Anesthesiology 2313: 2292: 2251: 2222:(5): 471–496. 2202: 2180: 2150: 2131: 2113: 2094: 2067: 2041: 2000: 1941: 1887: 1838: 1792: 1765:(5): 571–582. 1748: 1704: 1663: 1622: 1595:(2): 197–208. 1579: 1535: 1484: 1435: 1408: 1354: 1305: 1270: 1240: 1211:(3): 350–375. 1191: 1169: 1148:(3): 377–386. 1142:Carcinogenesis 1128: 1093: 1041: 992: 943: 894: 845: 838: 828:(in Spanish). 814: 765: 735: 705:Anesthesiology 690: 688: 685: 681:ubiquitination 622: 621:Neuroblastomas 619: 556:cardiovascular 544:osteoarthritis 530: 527: 512:prescribed by 503: 500: 490:when added to 442: 441:Research fraud 439: 390:cyclooxygenase 377:prostaglandins 340: 337: 335: 332: 308:boxed warnings 291: 288: 258: 255: 234: 231: 206: 203: 171: 168: 141:boxed warnings 80: 79: 62:September 2015 40:of the subject 38:worldwide view 33: 31: 24: 15: 13: 10: 9: 6: 4: 3: 2: 7136: 7125: 7122: 7120: 7117: 7115: 7112: 7111: 7109: 7094: 7093: 7089: 7087: 7086: 7082: 7079: 7078: 7075: 7069: 7063: 7061: 7055: 7053: 7050: 7048: 7045: 7043: 7040: 7038: 7035: 7033: 7032:Linoleic acid 7030: 7027: 7026: 7024: 7020: 7010: 7007: 7005: 7002: 7000: 6997: 6995: 6992: 6990: 6987: 6985: 6982: 6980: 6977: 6975: 6972: 6970: 6967: 6965: 6962: 6960: 6957: 6955: 6952: 6950: 6947: 6945: 6942: 6940: 6937: 6935: 6932: 6931: 6929: 6924: 6918: 6914: 6910: 6905: 6895: 6891: 6887: 6882: 6876: 6872: 6868: 6863: 6857: 6850: 6846: 6842: 6838: 6835: 6833: 6830: 6829: 6827: 6822: 6812: 6806: 6803: 6801: 6798: 6796: 6793: 6791: 6788: 6786: 6783: 6781: 6778: 6776: 6773: 6771: 6768: 6766: 6763: 6761: 6758: 6756: 6753: 6751: 6748: 6746: 6743: 6741: 6738: 6736: 6733: 6731: 6728: 6726: 6723: 6721: 6714: 6712: 6709: 6707: 6704: 6702: 6699: 6697: 6694: 6692: 6689: 6687: 6684: 6682: 6679: 6677: 6674: 6672: 6669: 6667: 6664: 6662: 6659: 6657: 6654: 6652: 6649: 6645: 6642: 6640: 6637: 6635: 6632: 6630: 6627: 6625: 6622: 6620: 6617: 6615: 6612: 6610: 6607: 6605: 6602: 6600: 6597: 6595: 6592: 6590: 6587: 6585: 6582: 6580: 6577: 6573: 6570: 6568: 6565: 6563: 6560: 6558: 6555: 6553: 6550: 6548: 6545: 6543: 6540: 6536: 6533: 6531: 6528: 6524: 6521: 6519: 6516: 6514: 6511: 6507: 6504: 6502: 6501:Fluproquazone 6499: 6498:Quinazolines: 6495: 6492: 6490: 6487: 6485: 6482: 6478: 6475: 6473: 6470: 6468: 6465: 6463: 6460: 6458: 6455: 6453: 6450: 6448: 6445: 6443: 6440: 6436: 6433: 6431: 6428: 6426: 6423: 6421: 6418: 6416: 6413: 6409: 6406: 6404: 6401: 6399: 6396: 6394: 6391: 6389: 6386: 6384: 6381: 6379: 6376: 6374: 6371: 6369: 6366: 6362: 6359: 6357: 6354: 6352: 6349: 6347: 6344: 6342: 6339: 6337: 6334: 6332: 6329: 6327: 6324: 6322: 6319: 6317: 6314: 6312: 6309: 6307: 6304: 6302: 6299: 6297: 6294: 6292: 6289: 6287: 6284: 6282: 6279: 6277: 6276:Flunoxaprofen 6274: 6272: 6269: 6267: 6264: 6262: 6261:Dexketoprofen 6259: 6257: 6256:Dexindoprofen 6254: 6252: 6249: 6247: 6244: 6242: 6239: 6237: 6234: 6232: 6229: 6227: 6224: 6220: 6217: 6215: 6212: 6210: 6207: 6205: 6202: 6200: 6197: 6195: 6194:Proglumetacin 6192: 6190: 6187: 6185: 6182: 6180: 6177: 6175: 6172: 6170: 6167: 6165: 6162: 6160: 6157: 6155: 6152: 6150: 6147: 6145: 6142: 6140: 6137: 6135: 6132: 6130: 6127: 6125: 6124:Difenpiramide 6122: 6120: 6117: 6115: 6112: 6110: 6107: 6105: 6102: 6100: 6097: 6095: 6092: 6090: 6087: 6085: 6082: 6080: 6077: 6075: 6072: 6070: 6067: 6065: 6062: 6061:Acetic acids: 6058: 6055: 6053: 6050: 6048: 6045: 6043: 6040: 6038: 6035: 6033: 6030: 6028: 6025: 6023: 6020: 6018: 6015: 6013: 6010: 6008: 6005: 6003: 6000: 5998: 5995: 5993: 5990: 5988: 5985: 5983: 5980: 5978: 5975: 5973: 5970: 5967: 5966: 5964: 5962: 5950: 5947: 5943: 5937: 5933: 5923: 5920: 5918: 5915: 5913: 5910: 5908: 5905: 5903: 5900: 5898: 5895: 5893: 5890: 5888: 5885: 5883: 5880: 5878: 5875: 5873: 5870: 5868: 5865: 5863: 5860: 5858: 5855: 5853: 5850: 5848: 5845: 5843: 5840: 5838: 5835: 5833: 5830: 5828: 5825: 5823: 5820: 5818: 5815: 5813: 5810: 5808: 5805: 5803: 5800: 5798: 5795: 5793: 5792:Fenprostalene 5790: 5788: 5785: 5783: 5780: 5778: 5775: 5773: 5770: 5768: 5765: 5763: 5760: 5758: 5755: 5753: 5750: 5748: 5745: 5743: 5742:Delprostenate 5740: 5738: 5735: 5733: 5730: 5728: 5725: 5723: 5720: 5718: 5715: 5714: 5712: 5708: 5702: 5699: 5697: 5694: 5692: 5689: 5687: 5684: 5682: 5679: 5677: 5674: 5672: 5669: 5667: 5664: 5662: 5659: 5657: 5654: 5652: 5649: 5647: 5641: 5639: 5636: 5634: 5631: 5629: 5626: 5624: 5621: 5619: 5616: 5614: 5611: 5609: 5606: 5604: 5601: 5599: 5596: 5594: 5591: 5589: 5586: 5584: 5581: 5579: 5576: 5574: 5571: 5569: 5566: 5564: 5561: 5559: 5556: 5554: 5551: 5549: 5546: 5544: 5541: 5539: 5536: 5533: 5532: 5529: 5526: 5524: 5521: 5519: 5515:Thromboxane A 5513: 5511: 5508: 5506: 5500: 5497: 5496: 5494: 5489: 5479: 5473: 5470: 5467: 5466: 5463: 5460: 5458: 5455: 5453: 5450: 5448: 5445: 5443: 5440: 5438: 5437:(alprostadil) 5431: 5429: 5422: 5420: 5417: 5415: 5412: 5410: 5407: 5405: 5402: 5400: 5397: 5395: 5392: 5390: 5387: 5385: 5382: 5380: 5377: 5375: 5372: 5369: 5368: 5366: 5361: 5351: 5345: 5342: 5340: 5337: 5335: 5332: 5330: 5327: 5325: 5318: 5316: 5310: 5308: 5305: 5303: 5300: 5298: 5295: 5293: 5290: 5288: 5285: 5283: 5280: 5278: 5275: 5272: 5271: 5269: 5264: 5254: 5244: 5241: 5239: 5236: 5234: 5227: 5225: 5222: 5220: 5217: 5215: 5212: 5210: 5207: 5205: 5202: 5200: 5197: 5195: 5189: 5186: 5185: 5183: 5179: 5173: 5170: 5168: 5165: 5163: 5160: 5158: 5155: 5152: 5151: 5148: 5145: 5143: 5136: 5134: 5133:(alprostadil) 5127: 5125: 5122: 5120: 5117: 5114: 5113: 5111: 5106: 5097: 5091: 5088: 5085: 5084: 5081: 5078: 5076: 5073: 5071: 5068: 5066: 5059: 5057: 5056:(alprostadil) 5050: 5048: 5042: 5040: 5037: 5035: 5032: 5030: 5027: 5025: 5022: 5020: 5017: 5015: 5012: 5010: 5007: 5005: 5002: 4999: 4998: 4996: 4991: 4982: 4976: 4973: 4971: 4968: 4966: 4963: 4960: 4959: 4956: 4953: 4951: 4944: 4942: 4941:(alprostadil) 4935: 4933: 4930: 4928: 4925: 4922: 4921: 4919: 4914: 4905: 4899: 4896: 4894: 4891: 4889: 4886: 4884: 4881: 4879: 4876: 4873: 4872: 4869: 4866: 4864: 4857: 4855: 4854:(alprostadil) 4848: 4846: 4843: 4841: 4838: 4836: 4833: 4831: 4828: 4826: 4823: 4821: 4818: 4815: 4814: 4812: 4807: 4798: 4795: 4790: 4780: 4770: 4767: 4765: 4762: 4760: 4757: 4755: 4752: 4750: 4747: 4745: 4742: 4740: 4737: 4735: 4732: 4730: 4727: 4725: 4722: 4720: 4717: 4715: 4712: 4709: 4708: 4705: 4699: 4697: 4694: 4691: 4690: 4688: 4683: 4674: 4668: 4665: 4663: 4660: 4658: 4655: 4652: 4651: 4648: 4645: 4643: 4637: 4634: 4633: 4631: 4626: 4617: 4614: 4609: 4599: 4596: 4592: 4586: 4582: 4578: 4575: 4572: 4565: 4560: 4558: 4553: 4551: 4546: 4545: 4542: 4526: 4523: 4522: 4520: 4518:Miscellaneous 4516: 4510: 4506: 4505: 4502: 4498: 4497: 4495: 4492: 4488: 4482: 4479: 4477: 4473: 4472: 4467: 4464: 4462: 4459: 4457: 4456:Enkephalinase 4454: 4453: 4452: 4449: 4445: 4442: 4440: 4437: 4436: 4435: 4434:Endopeptidase 4432: 4428: 4425: 4423: 4420: 4419: 4418: 4414: 4410: 4409: 4406: 4403: 4401: 4400:Neuraminidase 4398: 4396: 4392: 4391: 4388: 4385: 4383: 4380: 4378: 4374: 4373: 4371: 4368: 4364: 4354: 4351: 4350: 4349: 4346: 4345: 4344: 4341: 4337: 4334: 4332: 4329: 4328: 4327: 4323: 4322: 4319: 4315: 4314: 4311: 4308: 4306: 4302: 4301: 4298: 4294: 4293: 4290: 4287: 4285: 4281: 4280: 4278: 4275: 4271: 4265: 4262: 4260: 4256: 4255: 4252: 4249: 4247: 4243: 4242: 4239: 4235: 4234: 4231: 4227: 4226: 4223: 4219: 4218: 4215: 4211: 4210: 4207: 4204: 4202: 4198: 4197: 4195: 4192: 4188: 4185: 4181: 4175: 4172: 4170: 4167: 4165: 4162: 4160: 4157: 4155: 4152: 4151: 4149: 4145: 4141: 4137: 4130: 4125: 4123: 4118: 4116: 4111: 4110: 4107: 4095: 4091: 4087: 4085: 4077: 4075: 4067: 4066: 4063: 4058: 4054: 4050: 4046: 4040: 4034: 4031: 4029: 4026: 4024: 4021: 4019: 4016: 4014: 4011: 4009: 4006: 4004: 4001: 4000: 3998: 3992: 3986: 3983: 3981: 3978: 3976: 3973: 3971: 3968: 3966: 3963: 3961: 3958: 3956: 3953: 3951: 3948: 3946: 3943: 3941: 3940:Fluproquazone 3938: 3936: 3933: 3931: 3928: 3926: 3923: 3921: 3918: 3917: 3915: 3911: 3905: 3902: 3900: 3897: 3895: 3892: 3890: 3887: 3885: 3882: 3880: 3877: 3875: 3872: 3870: 3867: 3865: 3862: 3860: 3857: 3854: 3850: 3849: 3845: 3843: 3840: 3839: 3837: 3833: 3829: 3823: 3820: 3818: 3817:Niflumic acid 3815: 3813: 3810: 3808: 3807: 3803: 3801: 3798: 3796: 3793: 3791: 3788: 3786: 3783: 3781: 3778: 3776: 3773: 3771: 3768: 3766: 3763: 3761: 3758: 3757: 3755: 3752: 3746: 3742: 3736: 3732: 3731: 3727: 3725: 3722: 3720: 3717: 3715: 3712: 3710: 3707: 3705: 3702: 3700: 3697: 3695: 3692: 3690: 3687: 3685: 3682: 3680: 3677: 3675: 3674: 3670: 3668: 3665: 3663: 3660: 3658: 3655: 3653: 3650: 3648: 3645: 3643: 3642: 3638: 3636: 3633: 3631: 3630:Flunoxaprofen 3628: 3626: 3623: 3621: 3618: 3616: 3615:Dexketoprofen 3613: 3611: 3608: 3606: 3603: 3601: 3598: 3596: 3593: 3592: 3590: 3587: 3584:derivatives ( 3582: 3578: 3572: 3569: 3567: 3564: 3562: 3561: 3557: 3555: 3552: 3550: 3547: 3545: 3542: 3540: 3537: 3535: 3532: 3531: 3529: 3527: 3523: 3517: 3514: 3512: 3509: 3507: 3504: 3502: 3499: 3497: 3496:Proglumetacin 3494: 3492: 3491:Prodolic acid 3489: 3487: 3484: 3482: 3479: 3477: 3474: 3472: 3469: 3467: 3464: 3462: 3459: 3457: 3454: 3452: 3449: 3447: 3444: 3442: 3439: 3437: 3434: 3432: 3431:Difenpiramide 3429: 3427: 3426: 3422: 3420: 3417: 3415: 3412: 3410: 3407: 3405: 3402: 3400: 3397: 3395: 3392: 3390: 3387: 3385: 3382: 3381: 3379: 3374: 3370: 3364: 3361: 3359: 3356: 3354: 3351: 3349: 3346: 3344: 3341: 3339: 3336: 3334: 3331: 3329: 3326: 3324: 3321: 3319: 3316: 3314: 3311: 3309: 3306: 3304: 3301: 3299: 3296: 3294: 3293: 3289: 3288: 3286: 3284: 3280: 3274: 3271: 3269: 3266: 3264: 3261: 3259: 3258: 3254: 3252: 3249: 3247: 3244: 3242: 3239: 3237: 3234: 3232: 3229: 3227: 3224: 3222: 3219: 3217: 3214: 3212: 3209: 3207: 3204: 3202: 3199: 3197: 3194: 3192: 3189: 3187: 3184: 3183: 3181: 3179: 3178:pyrazolidines 3174: 3170: 3165: 3161: 3157: 3153: 3146: 3141: 3139: 3134: 3132: 3127: 3126: 3123: 3114: 3110: 3106: 3102: 3098: 3094: 3089: 3085: 3081: 3077: 3073: 3069: 3065: 3060: 3056: 3052: 3048: 3044: 3040: 3036: 3032: 3028: 3022: 3018: 3014: 3009: 3004: 3000: 2996: 2992: 2987: 2983: 2979: 2975: 2971: 2967: 2963: 2959: 2955: 2950: 2946: 2942: 2938: 2934: 2930: 2926: 2921: 2917: 2912: 2902:on 2007-07-08 2901: 2897: 2893: 2888: 2883: 2879: 2875: 2871: 2867: 2863: 2858: 2854: 2850: 2845: 2840: 2836: 2832: 2828: 2823: 2819: 2815: 2811: 2807: 2803: 2799: 2794: 2793: 2788: 2780: 2776: 2772: 2768: 2764: 2760: 2756: 2752: 2744: 2742: 2740: 2738: 2734: 2729: 2725: 2721: 2717: 2713: 2709: 2705: 2701: 2693: 2690: 2685: 2681: 2677: 2673: 2668: 2663: 2659: 2655: 2651: 2644: 2641: 2625: 2621: 2614: 2607: 2604: 2588: 2582: 2579: 2574: 2570: 2565: 2560: 2556: 2552: 2548: 2541: 2538: 2533: 2529: 2524: 2519: 2515: 2511: 2507: 2503: 2499: 2492: 2490: 2488: 2484: 2479: 2475: 2470: 2465: 2461: 2457: 2453: 2446: 2443: 2438: 2434: 2430: 2426: 2422: 2418: 2410: 2407: 2402: 2398: 2394: 2390: 2385: 2380: 2376: 2372: 2368: 2361: 2358: 2353: 2349: 2344: 2339: 2335: 2331: 2327: 2320: 2318: 2314: 2309: 2308: 2303: 2296: 2293: 2288: 2284: 2279: 2274: 2270: 2266: 2262: 2255: 2252: 2247: 2243: 2238: 2233: 2229: 2225: 2221: 2217: 2213: 2206: 2203: 2199: 2195: 2190: 2184: 2181: 2169: 2165: 2161: 2154: 2151: 2141: 2135: 2132: 2127: 2123: 2117: 2114: 2109: 2105: 2098: 2095: 2084: 2083: 2078: 2071: 2068: 2057:on 2009-02-03 2056: 2052: 2045: 2042: 2037: 2033: 2028: 2023: 2019: 2015: 2011: 2004: 2001: 1996: 1992: 1987: 1982: 1977: 1972: 1968: 1964: 1960: 1956: 1952: 1945: 1942: 1937: 1933: 1929: 1925: 1921: 1917: 1913: 1909: 1905: 1901: 1894: 1892: 1888: 1883: 1879: 1874: 1869: 1865: 1861: 1857: 1853: 1849: 1842: 1839: 1834: 1830: 1825: 1820: 1816: 1812: 1808: 1801: 1799: 1797: 1793: 1788: 1784: 1780: 1776: 1772: 1768: 1764: 1760: 1752: 1749: 1744: 1740: 1736: 1732: 1728: 1724: 1720: 1716: 1708: 1705: 1700: 1696: 1691: 1686: 1682: 1678: 1674: 1667: 1664: 1659: 1655: 1650: 1645: 1641: 1637: 1633: 1626: 1623: 1618: 1614: 1610: 1606: 1602: 1598: 1594: 1590: 1583: 1580: 1575: 1571: 1566: 1561: 1557: 1553: 1549: 1542: 1540: 1536: 1531: 1527: 1522: 1517: 1512: 1507: 1503: 1499: 1495: 1488: 1485: 1480: 1476: 1471: 1466: 1462: 1458: 1454: 1450: 1446: 1439: 1436: 1431: 1427: 1423: 1419: 1412: 1409: 1404: 1400: 1395: 1390: 1385: 1380: 1376: 1372: 1368: 1361: 1359: 1355: 1350: 1346: 1341: 1336: 1332: 1328: 1324: 1320: 1316: 1309: 1306: 1301: 1297: 1293: 1289: 1285: 1281: 1274: 1271: 1258: 1254: 1250: 1244: 1241: 1236: 1232: 1227: 1222: 1218: 1214: 1210: 1206: 1202: 1195: 1192: 1187: 1183: 1179: 1173: 1170: 1165: 1161: 1156: 1151: 1147: 1143: 1139: 1132: 1129: 1124: 1120: 1116: 1112: 1108: 1104: 1097: 1094: 1089: 1085: 1080: 1075: 1071: 1067: 1063: 1059: 1055: 1048: 1046: 1042: 1037: 1033: 1028: 1023: 1019: 1015: 1011: 1007: 1003: 996: 993: 988: 984: 979: 974: 970: 966: 962: 958: 954: 947: 944: 939: 935: 930: 925: 921: 917: 913: 909: 905: 898: 895: 890: 886: 881: 876: 872: 868: 864: 860: 856: 849: 846: 841: 839:84-8174-340-2 835: 831: 827: 826: 818: 815: 810: 806: 802: 798: 793: 788: 785:(2): 383–90. 784: 780: 779:FASEB Journal 776: 769: 766: 753: 749: 745: 739: 736: 732: 728: 724: 719: 714: 710: 706: 702: 695: 692: 686: 684: 682: 678: 674: 671: 667: 662: 660: 656: 652: 648: 644: 640: 636: 632: 631:neuroblastoma 628: 620: 618: 616: 612: 608: 604: 600: 596: 592: 588: 584: 579: 577: 573: 568: 563: 561: 557: 553: 549: 545: 541: 537: 528: 526: 524: 523: 517: 515: 510: 501: 499: 497: 493: 489: 485: 481: 480:spine surgery 477: 472: 468: 467:meta-articles 464: 460: 456: 452: 448: 440: 438: 436: 435:comorbidities 431: 427: 425: 421: 417: 413: 409: 404: 402: 398: 393: 391: 387: 383: 378: 374: 369: 367: 363: 359: 354: 352: 346: 338: 333: 331: 329: 325: 321: 317: 316:blood vessels 311: 309: 305: 301: 297: 289: 287: 284: 280: 276: 271: 268: 264: 257:Other targets 256: 254: 252: 248: 244: 243:schizophrenia 241:, as well as 240: 232: 230: 228: 227:breast cancer 224: 220: 216: 212: 204: 202: 200: 196: 192: 187: 185: 181: 177: 169: 167: 165: 161: 157: 155: 151: 147: 142: 138: 134: 128: 126: 122: 118: 114: 110: 106: 102: 98: 94: 90: 86: 76: 73: 65: 55: 51: 47: 41: 39: 32: 23: 22: 19: 7090: 7083: 7028: 6647: 6575: 6572:Propacetamol 6562:Parapropamol 6538: 6526: 6509: 6497: 6489:Floctafenine 6480: 6438: 6415:Azapropazone 6412:Pyrazolones: 6411: 6364: 6346:Tarenflurbil 6281:Flurbiprofen 6251:Dexibuprofen 6231:Benoxaprofen 6226:Alminoprofen 6222: 6149:Glucametacin 6060: 6037:Salicylamide 6027:Salacetamide 5968: 5917:Trimoprostil 5912:Tiprostanide 5897:Spiriprostil 5832:Naxaprostene 5782:Esuberaprost 5737:Cobiprostone 5535:Antagonists: 5534: 5498: 5469:Antagonists: 5468: 5462:Treprostinil 5370: 5302:Fluprostenol 5292:Cloprostenol 5273: 5187: 5154:Antagonists: 5153: 5119:Lubiprostone 5115: 5087:Antagonists: 5086: 5000: 4962:Antagonists: 4961: 4955:Treprostinil 4923: 4875:Antagonists: 4874: 4840:Lubiprostone 4816: 4711:Antagonists: 4710: 4692: 4654:Antagonists: 4653: 4647:Treprostinil 4635: 4450: 4417:Exopeptidase 4387:Ribonuclease 4353:Janus kinase 4238:Lipoxygenase 4214:5α-Reductase 4136:Pharmacology 4044: 3996:combinations 3846: 3812:Morniflumate 3804: 3775:Floctafenine 3760:Azapropazone 3744: 3728: 3704:Tarenflurbil 3689:Piketoprofen 3684:Pelubiprofen 3671: 3639: 3635:Flurbiprofen 3610:Dexibuprofen 3600:Benoxaprofen 3595:Alminoprofen 3558: 3423: 3353:Salicylamide 3290: 3255: 3231:Mofebutazone 3211:Famprofazone 3206:Difenamizole 3196:Azapropazone 3096: 3092: 3067: 3063: 3030: 3026: 2998: 2994: 2957: 2953: 2928: 2924: 2915: 2904:. 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Retrieved 1257:the original 1252: 1243: 1208: 1204: 1194: 1186:the original 1181: 1172: 1145: 1141: 1131: 1106: 1102: 1096: 1061: 1057: 1009: 1005: 995: 960: 956: 946: 911: 907: 897: 862: 858: 848: 824: 817: 782: 778: 768: 756:. Retrieved 747: 738: 730: 708: 704: 694: 663: 647:cellular DNA 624: 595:obstructions 591:perforations 580: 575: 566: 564: 551: 532: 520: 518: 505: 476:bone healing 447:Scott Reuben 444: 428: 405: 394: 386:biosynthesis 370: 365: 355: 348: 320:prostacyclin 312: 293: 283:cell culture 272: 260: 236: 215:precancerous 208: 188: 173: 170:Medical uses 158: 129: 109:inflammation 92: 88: 84: 83: 68: 59: 35: 18: 7029:Precursors: 6969:Nicogrelate 6949:Furegrelate 6890:Bimatoprost 6800:Trifenagrel 6790:Tiflamizole 6760:Rutecarpine 6745:Resveratrol 6686:Glimepiride 6651:Anitrazafen 6629:Robenacoxib 6609:Lumiracoxib 6542:Acetanilide 6484:Antrafenine 6442:Ampiroxicam 6336:Pranoprofen 6321:Naproxcinod 6214:Zidometacin 6139:Fenclofenac 6064:Aceclofenac 6002:Ethenzamide 5997:Dipyrocetyl 5892:Rosaprostol 5872:Posaraprost 5857:Penprostene 5847:Ornoprostil 5827:Mexiprostil 5822:Meteneprost 5777:Eptaloprost 5752:Dimoxaprost 5717:Arbaprostil 5671:Seratrodast 5563:BMS-180,291 5394:Carbacyclin 5344:Unoprostone 5324:(dinoprost) 5307:Latanoprost 5282:Bimatoprost 5277:Alfaprostol 5233:(dinoprost) 5172:ONO-AE3-208 5124:Misoprostol 5080:Sulprostone 5070:Remiprostol 5039:Misoprostol 5034:Latanoprost 5009:Carbacyclin 4970:PF-04418948 4932:Misoprostol 4868:Sulprostone 4845:Misoprostol 4835:Latanoprost 4769:Vidupiprant 4759:Timapiprant 4754:Setipiprant 4729:Fevipiprant 4696:Indometacin 4667:Vidupiprant 4662:Laropiprant 4466:Oxytocinase 4274:Transferase 3945:Glucosamine 3925:Benzydamine 3894:Robenacoxib 3879:Lumiracoxib 3770:Etofenamate 3735:Naproxcinod 3724:Zaltoprofen 3534:Ampiroxicam 3456:Indometacin 3384:Aceclofenac 3375:derivatives 3373:acetic acid 3323:Ethenzamide 3318:Dipyrocetyl 3283:salicylates 3173:pyrazolones 2265:Circulation 1811:Circulation 560:prophylaxis 160:Paracetamol 7108:Categories 6999:Samixogrel 6994:Rolafagrel 6979:Picotamide 6959:Midazogrel 6934:Camonagrel 6795:Timegadine 6740:Pamicogrel 6711:Licofelone 6691:Hyperforin 6656:Clobuzarit 6644:Valdecoxib 6639:Tilmacoxib 6624:Polmacoxib 6599:Etoricoxib 6567:Phenacetin 6535:Nimesulide 6513:Clonixeril 6506:Proquazone 6462:Lornoxicam 6361:Vedaprofen 6311:Miroprofen 6306:Loxoprofen 6301:Ketoprofen 6296:Indoprofen 6271:Fenoprofen 6184:Oxametacin 6179:Nabumetone 6119:Diclofenac 6114:Clometacin 6109:Cinmetacin 6104:Bumadizone 6084:Alclofenac 6069:Acemetacin 6007:Guacetisal 5992:Diflunisal 5942:inhibitors 5907:Tilsuprost 5887:Rivenprost 5882:Rioprostil 5877:Prostalene 5862:Pimilprost 5852:Oxoprostol 5842:Nocloprost 5817:Luprostiol 5807:Lanproston 5802:Froxiprost 5797:Flunoprost 5787:Etiproston 5772:Enisoprost 5767:Eganoprost 5727:Ciprostene 5696:Terutroban 5686:Sulotroban 5666:Samixogrel 5651:Ramatroban 5638:Picotamide 5623:Mipitroban 5618:Linotroban 5603:Imitrodast 5593:ICI-192605 5588:ICI-185282 5573:Domitroban 5553:Argatroban 5452:Taprostene 5374:ACT-333679 5339:Travoprost 5334:Tafluprost 5329:Sulotroban 5287:Carboprost 5243:Taprenepag 5224:Omidenepag 5219:Nocloprost 5209:Evatanepag 5204:Carboprost 5157:Grapiprant 4749:Ramatroban 4657:Asapiprant 4577:modulators 4571:Prostanoid 3975:Proquazone 3965:Nimesulide 3960:Nabumetone 3955:Hyperforin 3904:Valdecoxib 3869:Etoricoxib 3719:Vedaprofen 3667:Miroprofen 3662:Loxoprofen 3657:Ketoprofen 3652:Indoprofen 3625:Fenoprofen 3549:Lornoxicam 3486:Oxametacin 3425:Diclofenac 3419:Bumadizone 3394:Alclofenac 3389:Acemetacin 3328:Guacetisal 3313:Diflunisal 3303:Benorylate 3273:Suxibuzone 3241:Nifenazone 3226:Metamizole 2906:2008-09-01 2174:2015-05-23 2140:US 6048850 2088:2011-02-28 2061:2010-11-11 1642:(4): E21. 1182:Fact Sheet 687:References 615:IMS Health 540:diclofenac 455:pregabalin 451:gabapentin 430:Valdecoxib 219:anti-tumor 195:colchicine 176:etoricoxib 166:activity. 150:etoricoxib 7004:Terbogrel 6984:Pirmagrel 6944:Dazoxiben 6939:Dazmegrel 6832:Retinoids 6750:Romazarit 6696:Itazigrel 6681:FR-122047 6676:Flumizole 6634:Rofecoxib 6619:Parecoxib 6614:Mavacoxib 6604:Firocoxib 6594:Deracoxib 6589:Cimicoxib 6584:Celecoxib 6579:Apricoxib 6530:Flosulide 6494:Glafenine 6477:Tenoxicam 6472:Piroxicam 6467:Meloxicam 6351:Tepoxalin 6331:Pirprofen 6326:Oxaprozin 6291:Ibuproxam 6286:Ibuprofen 6246:Carprofen 6241:Butibufen 6219:Zomepirac 6189:Oxindanac 6174:Mofezolac 6169:Lonazolac 6164:Ketorolac 6144:Fentiazac 6099:Bufexamac 6094:Bromfenac 6074:Aclofenac 6057:Triflusal 6047:Salsalate 5972:Aloxiprin 5922:Viprostol 5867:Piriprost 5837:Nileprost 5812:Limaprost 5762:Ecraprost 5757:Doxaprost 5747:Deprostil 5732:Clinprost 5691:Terbogrel 5681:SQ-29,548 5676:SQ-28,668 5633:ONO-11120 5598:Ifetroban 5568:Daltroban 5558:Bay U3405 5528:Vapiprost 5499:Agonists: 5472:RO1138452 5447:Selexipag 5442:Ralinepag 5399:Cicaprost 5389:BMY-45778 5384:Beraprost 5371:Agonists: 5297:Enprostil 5274:Agonists: 5238:Simenepag 5214:Gemeprost 5188:Agonists: 5162:GW-627368 5116:Agonists: 5019:Enprostil 5014:Cicaprost 5004:Beraprost 5001:Agonists: 4927:Butaprost 4924:Agonists: 4825:Enprostil 4820:Beraprost 4817:Agonists: 4724:Bay U3405 4693:Agonists: 4636:Agonists: 4574:signaling 4367:Hydrolase 4331:Integrase 4246:Aromatase 4183:Substrate 4045:underline 3970:Oxaceprol 3935:Diacerein 3899:Rofecoxib 3889:Parecoxib 3884:Mavacoxib 3874:Firocoxib 3864:Deracoxib 3859:Cimicoxib 3853:+tramadol 3848:Celecoxib 3842:Apricoxib 3795:Glafenine 3790:Flutiazin 3751:fenamates 3709:Tepoxalin 3694:Pirprofen 3679:Oxaprozin 3647:Ibuproxam 3641:Ibuprofen 3605:Carprofen 3571:Tenoxicam 3566:Pivoxicam 3560:Piroxicam 3554:Meloxicam 3516:Zomepirac 3481:Mofezolac 3476:Lonazolac 3471:Ketorolac 3451:Fentiazac 3414:Bufexamac 3409:Bromfenac 3343:Salsalate 3298:Aloxiprin 3251:Phenazone 3216:Feprazone 3201:Clofezone 2945:195232705 2831:MedGenMed 2633:4 January 2596:4 January 2592:. Fda.gov 2261:"Aspirin" 611:marketing 536:ibuprofen 488:clonidine 484:ketorolac 412:meloxicam 373:inhibitor 267:analgesic 184:ibuprofen 180:celecoxib 146:parecoxib 137:celecoxib 133:Rofecoxib 125:rofecoxib 121:celecoxib 50:talk page 7080:See also 6989:Ridogrel 6964:Nafagrel 6954:Isbogrel 6837:Selenium 6805:Tropesin 6780:SC-58125 6765:Satigrel 6730:NCX-4040 6706:L-670596 6701:L-655240 6661:Curcumin 6523:Flunixin 6518:Clonixin 6457:Isoxicam 6452:Enolicam 6447:Droxicam 6425:Isopyrin 6420:Dipyrone 6341:Suprofen 6316:Naproxen 6266:Fenbufen 6209:Tolmetin 6199:Sulindac 6134:Felbinac 6129:Etodolac 6089:Bendazac 5902:Tiaprost 5722:Ataprost 5710:Unsorted 5656:Ridogrel 5628:ONO-3708 5613:L-670596 5608:L-655240 5583:GR-32191 5199:Aganepag 5181:Unsorted 5167:L-161982 5147:TCS-2510 5090:L-798106 4975:TG 4-155 4898:SC-51322 4893:SC-51089 4888:SC-19220 4883:ONO-8130 4719:AZD-1981 4714:ADC-3680 4585:Receptor 4413:Protease 4074:category 3835:(coxibs) 3785:Flunixin 3765:Clonixin 3699:Suprofen 3673:Naproxen 3620:Fenbufen 3544:Isoxicam 3539:Droxicam 3511:Tolmetin 3506:Tiopinac 3501:Sulindac 3466:Isoxepac 3441:Felbinac 3436:Etodolac 3404:Bendazac 3236:Morazone 3221:Kebuzone 3191:Ampyrone 3113:15668360 3084:15668363 3055:10865602 3047:15492235 3017:12641865 2982:34284072 2974:11280106 2896:12396942 2853:15208519 2837:(1): 6. 2818:11464731 2779:21996428 2771:16983334 2751:Oncogene 2728:10865602 2720:15492235 2684:10745161 2676:16339408 2573:11087881 2532:16893926 2478:11087881 2437:10979111 2393:21350225 2352:19934873 2287:10715270 2246:35685617 1936:36654810 1928:22700906 1882:16740558 1833:17325246 1787:21046732 1779:15846081 1743:34283027 1735:17431104 1699:16123214 1658:16709027 1617:21093404 1609:18230053 1574:12464646 1530:18485224 1479:17955049 1430:20047157 1403:31551825 1349:17971769 1300:16507393 1235:29578814 1164:19136477 1123:26057289 1088:34882311 1036:24150982 987:24809657 938:19821329 889:19588426 832:España. 830:Elsevier 801:17884974 752:Archived 645:. 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