PF-04457845

PF-04457845
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C23H20F3N5O2
Molar mass 455.432 g/mol
3D model (JSmol)

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

References

  1. 1 2 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. doi:10.1021/ml100190t. PMC 3109749. PMID 21666860.
  2. ↑ 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. doi:10.1124/jpet.111.180257. PMC 3126636. PMID 21505060.
  3. ↑ 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. doi:10.1111/j.1365-2125.2011.04137.x. PMC 3403198. PMID 22044402.
  4. ↑ A Study To Investigate Whether PF-04457845 Is Effective In Treating Pain, Is Safe And Tolerable In Patients With Osteoarthritis Of The Knee
  5. ↑ 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. doi:10.1016/j.pain.2012.04.020. PMID 22727500.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.