PF-04457845

• CAT Number: I000145
• CAS Number: 1020315-31-4
• Molecular Formula: C23H20F3N5O2
• Molecular Weight: 455.4
• Purity: ≥95%
• Synonyms: N-pyridazin-3-yl-4-[[3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]methylidene]piperidine-1-carboxamide
• Target: FAAH
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 7.2 nM
• InChI: InChI=1S/C23H20F3N5O2/c24-23(25,26)18-6-7-21(27-15-18)33-19-4-1-3-17(14-19)13-16-8-11-31(12-9-16)22(32)29-20-5-2-10-28-30-20/h1-7,10,13-15H,8-9,11-12H2,(H,29,30,32)
• InChIKey: BATCTBJIJJEPHM-UHFFFAOYSA-N
• SMILES: O=C(NC1=CC=CN=N1)N(CC/2)CCC2=CC3=CC=CC(OC4=CC=C(C(F)(F)F)C=N4)=C3

PF-04457845 (CAT: I000145) is a potent and highly selective inhibitor of fatty acid amide hydrolase (FAAH), an enzyme responsible for the degradation of endocannabinoids. By inhibiting FAAH, PF-04457845 increases the levels of endocannabinoids, such as anandamide, which can modulate pain and inflammation. In animal studies, PF-04457845 has demonstrated analgesic and anti-inflammatory effects comparable to naproxen, a nonsteroidal anti-inflammatory drug (NSAID). These findings suggest that PF-04457845 has the potential as a therapeutic agent for the treatment of pain and inflammatory conditions.

Reference

1:Blocking of fatty acid amide hydrolase activity with PF-04457845 in human brain: a positron emission tomography study with the novel radioligand [(11)C]CURB. Boileau I, Rusjan PM, Williams B, Mansouri E, Mizrahi R, De Luca V, Johnson DS, Wilson AA, Houle S, Kish SJ, Tong J.J Cereb Blood Flow Metab. 2015 Nov;35(11):1827-35. doi: 10.1038/jcbfm.2015.133. Epub 2015 Jun 17. PMID: 26082009 Free PMC Article
2:Synthesis and preclinical evaluation of [11C-carbonyl]PF-04457845 for neuroimaging of fatty acid amide hydrolase. Hicks JW, Parkes J, Sadovski O, Tong J, Houle S, Vasdev N, Wilson AA.Nucl Med Biol. 2013 Aug;40(6):740-6. doi: 10.1016/j.nucmedbio.2013.04.008. Epub 2013 May 31. PMID: 23731552 Free PMC Article
3: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. Huggins JP, Smart TS, Langman S, Taylor L, Young T.Pain. 2012 Sep;153(9):1837-46. doi: 10.1016/j.pain.2012.04.020. Epub 2012 Jun 21. PMID: 22727500
4:Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects. Li GL, Winter H, Arends R, Jay GW, Le V, Young T, Huggins JP.Br J Clin Pharmacol. 2012 May;73(5):706-16. doi: 10.1111/j.1365-2125.2011.04137.x. PMID: 22044402 Free PMC Article
5:Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor. Johnson DS, Stiff C, Lazerwith SE, Kesten SR, Fay LK, Morris M, Beidler D, Liimatta MB, Smith SE, Dudley DT, Sadagopan N, Bhattachar SN, Kesten SJ, Nomanbhoy TK, Cravatt BF, Ahn K.ACS Med Chem Lett. 2011 Feb 10;2(2):91-96. PMID: 21666860 Free PMC Article
6:Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain. 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.J Pharmacol Exp Ther. 2011 Jul;338(1):114-24. doi: 10.1124/jpet.111.180257. Epub 2011 Apr 19. PMID: 21505060 Free PMC Article