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.
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 <<
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 <<
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