PF-04457845
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 522480

CAS#: 1020315-31-4

Description: 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. 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, but was found to be ineffective.


Chemical Structure

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PF-04457845
CAS# 1020315-31-4

Theoretical Analysis

MedKoo Cat#: 522480
Name: PF-04457845
CAS#: 1020315-31-4
Chemical Formula: C23H20F3N5O2
Exact Mass: 455.15691
Molecular Weight: 455.44121
Elemental Analysis: C, 60.66; H, 4.43; F, 12.51; N, 15.38; O, 7.03

Price and Availability

Size Price Availability Quantity
5.0mg USD 220.0 2 Weeks
10.0mg USD 380.0 2 Weeks
25.0mg USD 760.0 2 Weeks
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Synonym: PF-04457845; PF 04457845; PF04457845; PF-4457845; PF 4457845; PF4457845.

IUPAC/Chemical Name: N-pyridazin-3-yl-4-[(3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl)methylidene]piperidine-1-carboxamide

InChi Key: BATCTBJIJJEPHM-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=C(N1CC/C(CC1)=C\C2=CC=CC(OC3=NC=C(C(F)(F)F)C=C3)=C2)NC4=NN=CC=C4

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 455.44121 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Lodola A, Castelli R, Mor M, Rivara S. Fatty acid amide hydrolase inhibitors: a patent review (2009 - 2014). Expert Opin Ther Pat. 2015 Nov;25(11):1247-66. doi: 10.1517/13543776.2015.1067683. Epub 2015 Sep 28. PubMed PMID: 26413912.

2: Boileau I, Rusjan PM, Williams B, Mansouri E, Mizrahi R, De Luca V, Johnson DS, Wilson AA, Houle S, Kish SJ, Tong J. 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. J Cereb Blood Flow Metab. 2015 Nov;35(11):1827-35. doi: 10.1038/jcbfm.2015.133. Epub 2015 Jun 17. PubMed PMID: 26082009.

3: Bryden LA, Nicholson JR, Doods H, Pekcec A. Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior and analgesic efficacy. Osteoarthritis Cartilage. 2015 Sep;23(9):1605-12. doi: 10.1016/j.joca.2015.05.001. Epub 2015 May 9. PubMed PMID: 25966657.

4: Benson N, Metelkin E, Demin O, Li GL, Nichols D, van der Graaf PH. A systems pharmacology perspective on the clinical development of Fatty Acid amide hydrolase inhibitors for pain. CPT Pharmacometrics Syst Pharmacol. 2014 Jan 15;3:e91. doi: 10.1038/psp.2013.72. PubMed PMID: 24429592; PubMed Central PMCID: PMC3910012.

5: Hicks JW, Parkes J, Sadovski O, Tong J, Houle S, Vasdev N, Wilson AA. Synthesis and preclinical evaluation of [11C-carbonyl]PF-04457845 for neuroimaging of fatty acid amide hydrolase. Nucl Med Biol. 2013 Aug;40(6):740-6. doi: 10.1016/j.nucmedbio.2013.04.008. Epub 2013 May 31. PubMed PMID: 23731552; PubMed Central PMCID: PMC3737387.

6: Leung K. 4-(3-((5-(2-[(18)F]Fluoroethoxy)pyridine-2-yl)oxy)benzylidene)-N-(pyridazin-3-yl) piperidine-1-carboxamide. 2012 Oct 20 [updated 2013 Feb 07]. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK117245/ PubMed PMID: 23409304.

7: Di Marzo V. Inhibitors of endocannabinoid breakdown for pain: not so FA(AH)cile, after all. Pain. 2012 Sep;153(9):1785-6. doi: 10.1016/j.pain.2012.06.016. Epub 2012 Jul 10. PubMed PMID: 22785079.

8: Huggins JP, Smart TS, Langman S, Taylor L, Young T. 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. 2012 Sep;153(9):1837-46. doi: 10.1016/j.pain.2012.04.020. Epub 2012 Jun 21. PubMed PMID: 22727500.

9: Skaddan MB, Zhang L, Johnson DS, Zhu A, Zasadny KR, Coelho RV, Kuszpit K, Currier G, Fan KH, Beck EM, Chen L, Drozda SE, Balan G, Niphakis M, Cravatt BF, Ahn K, Bocan T, Villalobos A. The synthesis and in vivo evaluation of [18F]PF-9811: a novel PET ligand for imaging brain fatty acid amide hydrolase (FAAH). Nucl Med Biol. 2012 Oct;39(7):1058-67. doi: 10.1016/j.nucmedbio.2012.03.011. Epub 2012 May 8. PubMed PMID: 22571907; PubMed Central PMCID: PMC3611965.

10: Sasso O, Bertorelli R, Bandiera T, Scarpelli R, Colombano G, Armirotti A, Moreno-Sanz G, Reggiani A, Piomelli D. Peripheral FAAH inhibition causes profound antinociception and protects against indomethacin-induced gastric lesions. Pharmacol Res. 2012 May;65(5):553-63. doi: 10.1016/j.phrs.2012.02.012. Epub 2012 Mar 7. PubMed PMID: 22420940; PubMed Central PMCID: PMC3738192.

11: Li GL, Winter H, Arends R, Jay GW, Le V, Young T, Huggins JP. Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects. Br J Clin Pharmacol. 2012 May;73(5):706-16. doi: 10.1111/j.1365-2125.2011.04137.x. PubMed PMID: 22044402; PubMed Central PMCID: PMC3403198.

12: 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. Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor. ACS Med Chem Lett. 2011 Feb 10;2(2):91-96. PubMed PMID: 21666860; PubMed Central PMCID: PMC3109749.

13: 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. Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain. J Pharmacol Exp Ther. 2011 Jul;338(1):114-24. doi: 10.1124/jpet.111.180257. Epub 2011 Apr 19. PubMed PMID: 21505060; PubMed Central PMCID: PMC3126636.