PF-04457845
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Formula | C23H20F3N5O2 |
Molar mass | 455.432 g/mol |
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PF-04457845 is a potent and exquisitely selective inhibitor of the enzyme fatty acid amide hydrolase (FAAH), with an IC50 of 7.2nM, and both analgesic and antiinflammatory effects in animal studies comparable to naproxen.[1]
It has been well tolerated in human trials even at high dose ranges with no evidence for cognitive dysfunction, and has completed Phase II clinical trials for the treatment of osteoarthritis,[1][2][3][4] but was found to be ineffective.[5]
See also[edit]
- FAAH inhibitor
- 4-Nonylphenylboronic acid
- LY-2183240
- URB-597
- BIA 10-2474, problems in phase 1
References[edit]
- ^ a b Johnson, D. S.; Stiff, C.; Lazerwith, S. E.; Kesten, S. R.; Fay, L. K.; Morris, M.; Beidler, D.; Liimatta, M. B.; Smith, S. E.; Dudley, D. T.; Sadagopan, N.; Bhattachar, S. N.; Kesten, S. J.; Nomanbhoy, T. K.; Cravatt, B. F.; Ahn, K. (2011). "Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor". ACS Medicinal Chemistry Letters. 2 (2): 91–96. PMC 3109749 . PMID 21666860. doi:10.1021/ml100190t.
- ^ Ahn, K; Smith, SE; Liimatta, MB; Beidler, D; Sadagopan, N; Dudley, DT; Young, T; Wren, P; Zhang, Y; Swaney, S; Van Becelaere, K; Blankman, JL; Nomura, DK; Bhattachar, SN; Stiff, C; Nomanbhoy, TK; Weerapana, E; Johnson, DS; Cravatt, BF (Jul 2011). "Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain". Journal of Pharmacology and Experimental Therapeutics. 338 (1): 114–24. PMC 3126636 . PMID 21505060. doi:10.1124/jpet.111.180257.
- ^ Li, G. L.; Winter, H.; Arends, R.; Jay, G. W.; Le, V.; Young, T.; Huggins, J. P. (2012). "Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects". British Journal of Clinical Pharmacology. 73 (5): 706–716. PMID 22044402. doi:10.1111/j.1365-2125.2011.04137.x.
- ^ A Study To Investigate Whether PF-04457845 Is Effective In Treating Pain, Is Safe And Tolerable In Patients With Osteoarthritis Of The Knee
- ^ Huggins, J. P.; Smart, T. S.; Langman, S.; Taylor, L.; Young, T. (2012). "An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee". Pain. 153 (9): 1837. PMID 22727500. doi:10.1016/j.pain.2012.04.020.