1210004-12-8

JZL195 is a selective and efficacious dual FAAH/MAGL inhibitor with IC50 of 13 nM and 19 nM for mouse brain FAAH and MAGL respectively.IC50 value: 13 nM/19 nM (mouse brain FAAH/MAGL) [1]Target: dual FAAH/MAGL inhibitorin vitro: JZL195 shows only modest and incomplete inhibitory activity against NTE (IC50 >5 uM). At higher concentrations, JZL195 inhibited ABHD6 but not any of the other brain serine hydrolases detected in our competitive ABPP assays. JZL195 also inhibited rat and human FAAH and MAGL enzymes with IC50 values in the range of 10–100 nM based on competitive ABPP assays [1].in vivo: A time course analysis of mice given one administration ofJZL195 (20 mg/kg, i.p.) revealed that blockade of FAAH andMAGL lasted at least 10 h as judged by gel-based ABPP or AEAand 2-AG hydrolysis assays [1]. The effect of systemic injections of a range of doses of JZL195 and the pan-cannabinoid receptor agonist WIN55212 were performed 1 day following intraplantar injection of CFA in C57BL/6 mice. JZL195 and WIN55212 both reduced mechanical allodynia and thermal hyperalgesia, and produced catalepsy and sedation in a dose dependent manner. Unlike WIN55212, JZL195 reduced allodynia at doses below those at which side-effects were observed [2].