Fatty acid amides (FAA) are a diverse group of lipid mediators including arachidonoyl ethanolamide (AEA), oleoyl ethanolamide (OEA), palmitoyl ethanolamide (PEA) and N-arachidonoyl glycine. FAAs are hydrolyzed by several different enzymes with different substrate preferences. The metabolizing enzymes that hydrolyze FAA include fatty acid amide hydrolase (FAAH), and N-acylethanolamine-hydrolyzing acid amidase[3]. JNJ-1661010 is a selective inhibitor of FAAH with IC50 of 10 nM (rat) and 12 nM (human)[3]. The level of FAAH activity in the rat brain was decreased by at least 85% for up to 4 h after intraperitoneal dosing of 20 mg/kg JNJ-1661010, and only 25% of FAAH activity had returned by 24 h postdose, compared to control levels[3]. Treatment of wild-type mice with 10 mg/kg JNJ-1661010, intraperitoneally four times a day, resulted in prominent exacerbation of bleomycin-induced fibrosis and dermal thickening, myofibroblast counts and hydroxyproline content are significantly increased compared with sham-treated, bleomycin-challenged mice[4].
作用机制
The acyl piperazinyl fragment of JNJ-1661010 forms a covalent bond with the FAAH.
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