Redafamdastat

产品说明书

Print
Chemical Structure| 1020315-31-4 同义名 : PF-04457845; PF-4457845; PF4457845, redafamdastat
CAS号 : 1020315-31-4
货号 : A137082
分子式 : C23H20F3N5O2
纯度 : 98%
分子量 : 455.43
MDL号 : MFCD18782721
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(230.55 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
描述 Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase that degrades the fatty acid amide family of signaling lipids, including the endocannabinoid anandamide[3]. PF-04457845 selectively inhibits FAAH with an IC50 of 7.2 nM[3]. Men aged 18–55 years with cannabis dependence were treated with PF-04457845 (4 mg per day), and they showed reduced symptoms of cannabis withdrawal, lower self-reported cannabis use and lower urinary THC-COOH concentrations, compared with placebo group[4]. Osteoarthritis patients administrated with 4 mg q.d. PF-04457845 showed decreased FAAH activity by >96% and significantly increased 4 endogenous substrates (fatty acid amides). PF-04457845 was well tolerated in osteoarthritis patients, and there was no evidence of cannabinoid-type adverse events, but failed to induce effective analgesia[5].
作用机制 PF-04457845 inhibits FAAH by a covalent, irreversible mechanism involving carbamylation of the active-site serine nucleophile of FAAH.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

10.98mL

2.20mL

1.10mL

21.96mL

4.39mL

2.20mL
参考文献

[1]Johnson DS, Stiff C, et al. 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.

[2]Ahn K, Smith SE, et al. 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.

[3]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.

[4]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.

[5]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):1837-1846. doi: 10.1016/j.pain.2012.04.020. Epub 2012 Jun 21. PMID: 22727500.