ABX-1431 (C09-0735-659)

InformationABX-1431 ABX-1431 is a highly potent, selective, and CNS-penetrant Monoacylglycerol lipase (MGLL) inhibitor with IC50 values of 14 nM and 27 nM for hMGLL and mMGLL respectively.TargetshMGLL ; mMGLL 14 nM; 27 nMIn vitroABX-1431 is a potent human MGLL inhibitor (average IC50 = 0.014 μM) with >100-fold selectivity against ABHD6 and >200-fold selectivity against PLA2G7. Treatment of intact human PC3 cells with ABX-1431 following a 30 min inhibitor incubation time causes concentration dependent inhibition of MGLL activity with an IC50 value of 0.0022 μM, which is ∼6-fold more potent than that observed in vitro. ABX-1431 inhibits MGLL via carbamoylation of the catalytic nucleophile Ser122.In vivoPharmacokinetic analysis in rats and dogs of ABX-1431 indicate low to moderate systemic clearance, moderate volume of distribution, and high oral bioavailability (64% in rat, 57% in dog). While ABX-1431 is stable in human and dog plasma, it is not stable in rat plasma. ABX-1431 is a potent and selective inhibitor of MGLL in mouse and rat brain in vivo. ABX-1431 inhibits MGLL activity with an ED50 of 0.5-1.4 mg/kg (po) and dose-dependently increases brain 2-AG levels in mouse brain. A rat inflammatory pain model is used to assess the pharmacodynamics effect. ABX-1431 demonstrates potent antinociceptive effects in a formalin paw test at a dose that produced near complete MGLL inhibition and maximal elevation of 2-AG.Cell Research(from reference)Cell lines：PC3 cells Concentrations：0.1-10 μM Incubation Time：30 min. Specification: 0.98 Molecular Formula: C20H22F9N3O2 Molecular Weight: 507.39 EC Number: 870-188-4 PubChem CID: 71657619 Isomeric SMILES: C1CCN(C1)C2=C(C=CC(=C2)C(F)(F)F)CN3CCN(CC3)C(=O)OC(C(F)(F)F)C(F)(F)F Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/A414203-SCI_03b16af84cacb91c5cb8ac63aa42e484.pdf