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URB-597

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Chemical Structure| 546141-08-6 同义名 : KDS-4103
CAS号 : 546141-08-6
货号 : A724051
分子式 : C20H22N2O3
纯度 : 99%
分子量 : 338.4
MDL号 : MFCD05863934
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(310.28 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
动物实验配方：

5%DMSO+40%PEG300+5%Tween80+water 1 mg/mL

生物活性
靶点

  • FAAH

    FAAH, IC50:4.6 nM
描述 Fatty acid amide hydrolase (FAAH), an integral membrane bound enzyme, are intracellular enzymes responsible for the hydrolysis of endogenous fatty acid ethanolamides (FAEs). URB-597 (KDS-4103) is FAAH inhibitor with IC50 of 4.6 nM without effect on other cannabinoid-related targets[3]. Treatment with 10 μM URB-597 in microglial cells reduced the release of PGE2 to approximately 50% of control, and inhibited LPS stimulated TNF and NO release and iNOS expression[4]. In vivo, URB-597 (0.3 mg/kg/day, intraperitoneal (i.p.) injection) treatment in chronic cerebral hypoperfusion model inhibited impaired autophagy degradation and the disruption of beclin-1/Bcl-2 complex and subsequently cut off BNIP3-cyt C- and parkin-required mitophagy, finally preventing the abnormal excessive autophagy and mitophagy[5].
作用机制 Carbamoyl group in URB-597 may form two distinct hydrogen bonds with FAAH: one as an acceptor, with the hydroxyl group of Thr488, and the other as a donor, with the main chain carbonyl group of Leu192.
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00916201 Schizophrenia Phase 1 Not yet recruiting December 2020 Germany ... 展开 >> Dep. of Psychiatry and Psychotherapy, Central Institute of Mental Health Not yet recruiting Mannheim, BW, Germany, 68159 Contact: F. Markus Leweke, MD    +49 621 1703 ext 2321    leweke@cimh.de    Contact: Cathrin Rohleder, PhD    +49 621 1703 ext 2333    rohleder@cimh.de    Sub-Investigator: J. Malte Bumb, MD          Sub-Investigator: Cathrin Rohleder, PhD          Sub-Investigator: Till van der List, MD          Sub-Investigator: Juliane K. Mueller, MD          Sub-Investigator: Frank Enning, MD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.96mL

0.59mL

0.30mL

14.78mL

2.96mL

1.48mL

29.55mL

5.91mL

2.96mL
参考文献

[1]Tham CS, Whitaker J, et al. Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated release of inflammatory mediators. FEBS Lett. 2007 Jun 26;581(16):2899-904.

[2]Mor M, Rivara S, et al. Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies. J Med Chem. 2004 Oct 7;47(21):4998-5008.

[3]Mor M, Rivara S, Lodola A, Plazzi PV, Tarzia G, Duranti A, Tontini A, Piersanti G, Kathuria S, Piomelli D. Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies. J Med Chem. 2004 Oct 7;47(21):4998-5008. doi: 10.1021/jm031140x. PMID: 15456244.

[4]Tham CS, Whitaker J, Luo L, Webb M. Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated release of inflammatory mediators. FEBS Lett. 2007 Jun 26;581(16):2899-904. doi: 10.1016/j.febslet.2007.05.037. Epub 2007 May 25. PMID: 17543306.

[5]Su SH, Wu YF, Wang DP, Hai J. Inhibition of excessive autophagy and mitophagy mediates neuroprotective effects of URB597 against chronic cerebral hypoperfusion. Cell Death Dis. 2018 Jun 28;9(7):733. doi: 10.1038/s41419-018-0755-y. PMID: 29955058; PMCID: PMC6023888.