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MedKoo Cat#: 522480 | Name: PF-04457845
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Description:

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

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

PF-04457845
CAS#1020315-31-4

Theoretical Analysis

MedKoo Cat#: 522480

Name: PF-04457845

CAS#: 1020315-31-4

Chemical Formula: C23H20F3N5O2

Exact Mass: 455.1569

Molecular Weight: 455.44

Elemental Analysis: C, 60.66; H, 4.43; F, 12.51; N, 15.38; O, 7.03

Price and Availability

Size Price Availability Quantity
10mg USD 290.00 2 Weeks
25mg USD 580.00 2 Weeks
50mg USD 950.00 2 Weeks
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Synonym
PF-04457845; PF 04457845; PF04457845; PF-4457845; PF 4457845; PF4457845, redafamdastat
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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-04457845 is a FAAH inhibitor with IC50 values is 7.2±0.63 nM and 7.4±0.62 nM for hFAAH and rFAAH.
In vitro activity:
Correspondingly, a selective FAAH inhibitor, PF-04457845, inhibited the transforming growth factor-beta 1 (TGF-β1)-induced profibrogenic markers in human proximal tubular cell line (HK-2 cells) and mouse primary cultured tubular cells. Knockdown of FAAH by siRNA in HK-2 cells had similar effects as PF-04457845. Reference: Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166456. https://pubmed.ncbi.nlm.nih.gov/35710061/
In vivo activity:
Moreover, intragastric administration of the FAAH inhibitor PF-04457845(PF) ameliorated ovariectomy (OVX)-induced bone loss in mice. Further investigation revealed that nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were inhibited by PF treatment and FAAH knockdown. RNAseq indicated that the IL17 pathway was blocked by PF, and administration of recombinant murine IL17 protein could partially restore osteoclastogenesis and activate NF-κB and MAPK pathways. Reference: FASEB J. 2023 Jan;37(1):e22690. https://pubmed.ncbi.nlm.nih.gov/36468880/
Solvent mg/mL mM comments
Solubility
DMF 25.0 54.89
DMF:PBS (pH 7.2) (1:5) 0.2 0.35
DMSO 64.1 140.82
Ethanol 6.0 13.25
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 455.44 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
Formulation protocol:
1. Chen C, Wang W, Poklis JL, Lichtman AH, Ritter JK, Hu G, Xie D, Li N. Inactivation of fatty acid amide hydrolase protects against ischemic reperfusion injury-induced renal fibrogenesis. Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166456. doi: 10.1016/j.bbadis.2022.166456. Epub 2022 Jun 13. PMID: 35710061. 2. 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. doi: 10.1021/ml100190t. PMID: 21666860; PMCID: PMC3109749. 3. Zhu M, Guo Q, Kang H, Peng R, Dong Y, Zhang Y, Wang S, Liu H, Zhao H, Dong Z, Song K, Xu S, Wang P, Chen L, Liu J, Li F. Inhibition of FAAH suppresses RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway. FASEB J. 2023 Jan;37(1):e22690. doi: 10.1096/fj.202200911R. PMID: 36468880. 4. 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. PMID: 21505060; PMCID: PMC3126636.
In vitro protocol:
1. Chen C, Wang W, Poklis JL, Lichtman AH, Ritter JK, Hu G, Xie D, Li N. Inactivation of fatty acid amide hydrolase protects against ischemic reperfusion injury-induced renal fibrogenesis. Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166456. doi: 10.1016/j.bbadis.2022.166456. Epub 2022 Jun 13. PMID: 35710061. 2. 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. doi: 10.1021/ml100190t. PMID: 21666860; PMCID: PMC3109749.
In vivo protocol:
1. Zhu M, Guo Q, Kang H, Peng R, Dong Y, Zhang Y, Wang S, Liu H, Zhao H, Dong Z, Song K, Xu S, Wang P, Chen L, Liu J, Li F. Inhibition of FAAH suppresses RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway. FASEB J. 2023 Jan;37(1):e22690. doi: 10.1096/fj.202200911R. PMID: 36468880. 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. 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. PMID: 21505060; PMCID: PMC3126636.
1: Shamabadi A, Arabzadeh Bahri R, Karimi H, Heidari E, Akhondzadeh S. Emerging pharmacotherapy for the treatment of cannabis use disorder. Expert Opin Pharmacother. 2024 Apr;25(6):695-703. doi: 10.1080/14656566.2024.2353638. Epub 2024 May 15. PMID: 38717605. 2: Wen J, Sackett S, Tanaka M, Zhang Y. Therapeutic Effects of Combined Treatment with the AEA Hydrolysis Inhibitor PF04457845 and the Substrate Selective COX-2 Inhibitor LM4131 in the Mouse Model of Neuropathic Pain. Cells. 2023 Apr 27;12(9):1275. doi: 10.3390/cells12091275. PMID: 37174675; PMCID: PMC10177584. 3: Chen C, Wang W, Raymond M, Ahmadinejad F, Poklis JL, Em B, Gewirtz DA, Lichtman AH, Li N. Genetic Knockout of Fatty Acid Amide Hydrolase Ameliorates Cisplatin-Induced Nephropathy in Mice. Mol Pharmacol. 2023 Apr;103(4):230-240. doi: 10.1124/molpharm.122.000618. Epub 2023 Jan 26. PMID: 36702548; PMCID: PMC10029825. 4: Zhu M, Guo Q, Kang H, Peng R, Dong Y, Zhang Y, Wang S, Liu H, Zhao H, Dong Z, Song K, Xu S, Wang P, Chen L, Liu J, Li F. Inhibition of FAAH suppresses RANKL- induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway. FASEB J. 2023 Jan;37(1):e22690. doi: 10.1096/fj.202200911R. PMID: 36468880. 5: Punt JM, van der Vliet D, van der Stelt M. Chemical Probes to Control and Visualize Lipid Metabolism in the Brain. Acc Chem Res. 2022 Nov 15;55(22):3205-3217. doi: 10.1021/acs.accounts.2c00521. Epub 2022 Oct 25. PMID: 36283077; PMCID: PMC9670861. 6: Zhu Y, Zhang H, Mao H, Zhong S, Huang Y, Chen S, Yan K, Zhao Z, Hao X, Zhang Y, Yao H, Huang X, Wang M, Zhang W, Li J, Meng G, Qin X, Ye Z, Shen J, Song Y, Xu Y, Yang Z, Wang L, Zhang Y, Wen L. FAAH served a key membrane-anchoring and stabilizing role for NLRP3 protein independently of the endocannabinoid system. Cell Death Differ. 2023 Jan;30(1):168-183. doi: 10.1038/s41418-022-01054-4. Epub 2022 Sep 14. PMID: 36104448; PMCID: PMC9883386. 7: Vuilleumier C, Scherbaum N, Bonnet U, Roser P. Cannabinoids in the Treatment of Cannabis Use Disorder: Systematic Review of Randomized Controlled Trials. Front Psychiatry. 2022 Jun 22;13:867878. doi: 10.3389/fpsyt.2022.867878. PMID: 35815028; PMCID: PMC9256935. 8: Chen C, Wang W, Poklis JL, Lichtman AH, Ritter JK, Hu G, Xie D, Li N. Inactivation of fatty acid amide hydrolase protects against ischemic reperfusion injury-induced renal fibrogenesis. Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166456. doi: 10.1016/j.bbadis.2022.166456. Epub 2022 Jun 13. PMID: 35710061; PMCID: PMC10215004. 9: Alugubelly N, Mohammed AN, Carr RL. Persistent proteomic changes in glutamatergic and GABAergic signaling in the amygdala of adolescent rats exposed to chlorpyrifos as juveniles. Neurotoxicology. 2021 Jul;85:234-244. doi: 10.1016/j.neuro.2021.05.012. Epub 2021 May 28. PMID: 34058248; PMCID: PMC8276847. 10: Carr RL, Alugubelly N, de Leon K, Loyant L, Mohammed AN, Patterson ME, Ross MK, Rowbotham NE. Inhibition of fatty acid amide hydrolase by chlorpyrifos in juvenile rats results in altered exploratory and social behavior as adolescents. Neurotoxicology. 2020 Mar;77:127-136. doi: 10.1016/j.neuro.2020.01.002. Epub 2020 Jan 10. PMID: 31931040; PMCID: PMC7986983. 11: Bonifácio MJ, Sousa F, Aires C, Loureiro AI, Fernandes-Lopes C, Pires NM, Palma PN, Moser P, Soares-da-Silva P. Preclinical pharmacological evaluation of the fatty acid amide hydrolase inhibitor BIA 10-2474. Br J Pharmacol. 2020 May;177(9):2123-2142. doi: 10.1111/bph.14973. Epub 2020 Feb 12. PMID: 31901141; PMCID: PMC7161550. 12: Mayo LM, Asratian A, Lindé J, Morena M, Haataja R, Hammar V, Augier G, Hill MN, Heilig M. Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial. Biol Psychiatry. 2020 Mar 15;87(6):538-547. doi: 10.1016/j.biopsych.2019.07.034. Epub 2019 Aug 13. PMID: 31590924. 13: Galaj E, Xi ZX. Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders. CNS Drugs. 2019 Oct;33(10):1001-1030. doi: 10.1007/s40263-019-00664-w. PMID: 31549358; PMCID: PMC7451396. 14: Giacovazzo G, Bisogno T, Piscitelli F, Verde R, Oddi S, Maccarrone M, Coccurello R. Different Routes to Inhibit Fatty Acid Amide Hydrolase: Do All Roads Lead to the Same Place? Int J Mol Sci. 2019 Sep 11;20(18):4503. doi: 10.3390/ijms20184503. PMID: 31514437; PMCID: PMC6771131. 15: Nielsen S, Sabioni P, Gowing L, Le Foll B. Pharmacotherapies for Cannabis Use Disorders: Clinical Challenges and Promising Therapeutic Agents. Handb Exp Pharmacol. 2020;258:355-372. doi: 10.1007/164_2019_258. PMID: 31375922. 16: D'Souza DC, Cortes-Briones J, Creatura G, Bluez G, Thurnauer H, Deaso E, Bielen K, Surti T, Radhakrishnan R, Gupta A, Gupta S, Cahill J, Sherif MA, Makriyannis A, Morgan PT, Ranganathan M, Skosnik PD. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry. 2019 Jan;6(1):35-45. doi: 10.1016/S2215-0366(18)30427-9. Epub 2018 Dec 6. PMID: 30528676. 17: George TP. FAAH inhibition for treatment of problematic cannabis use. Lancet Psychiatry. 2019 Jan;6(1):3-4. doi: 10.1016/S2215-0366(18)30462-0. Epub 2018 Dec 6. PMID: 30528675. 18: Selvaraj P, Wen J, Tanaka M, Zhang Y. Therapeutic Effect of a Novel Fatty Acid Amide Hydrolase Inhibitor PF04457845 in the Repetitive Closed Head Injury Mouse Model. J Neurotrauma. 2019 May 15;36(10):1655-1669. doi: 10.1089/neu.2018.6226. Epub 2019 Jan 30. PMID: 30526351. 19: Bhuniya D, Kharul RK, Hajare A, Shaikh N, Bhosale S, Balwe S, Begum F, De S, Athavankar S, Joshi D, Madgula V, Joshi K, Raje AA, Meru AV, Magdum A, Mookhtiar KA, Barbhaiya R. Discovery and evaluation of novel FAAH inhibitors in neuropathic pain model. Bioorg Med Chem Lett. 2019 Jan 15;29(2):238-243. doi: 10.1016/j.bmcl.2018.11.048. Epub 2018 Nov 24. PMID: 30503633. 20: Tani Y, Sato M, Yokoyama M, Yokoyama M, Takahashi T, Toyoda E, Okada E, Fujimura S, Maruki H, Kato Y, Yamato M, Okano T, Mochida J. Intra-articular administration of EP2 enhances the articular cartilage repair in a rabbit model. J Tissue Eng Regen Med. 2018 Nov;12(11):2179-2187. doi: 10.1002/term.2748. Epub 2018 Sep 4. PMID: 30075064.