KT185

KT185 is an orally bioavailable inhibitor of alpha/beta-hydrolase domain-containing protein 6 (ABHD6) with an IC50 value of 0.21 nM in a competitive activity-based protein profiling assay using Neuro2A membranes. It inhibits ABHD6 in a 2-arachidonoyl glycerol (2-AG, Cay-62160) hydrolysis assay (IC50 = 13.6 nM for the mouse recombinant enzyme expressed in HEK293T cells). KT185 is selective for ABHD6 over diacylglycerol lipase beta (DAGLbeta) at 1 µM but inhibits lysophospholipase 1 (LYPLA1) and LYPLA2 at 10 µM. It inhibits ABHD6 activity in mouse liver and brain in vivo when administered at doses of 5-10 and approximately 40 mg/kg, respectively, without inhibiting fatty acid amide hydrolase (FAAH) in the brain. KT185 inhibits increases in the frequency of spontaneous inhibitory post-synaptic currents (sIPSCs) induced by nicotine (Cay-29138) in the rat ventral tegmental area (VTA) but does not reduce nicotine self-administration in rats when administered intracerebroventricularly at a dose of 200 µg. It has been used as a negative control for the off-target effect of the DAGL inhibitor KT172 (Cay-19112) on ABHD6.Formal Name: [4'-[1-[(2-phenyl-1-piperidinyl)carbonyl]-1H-1,2,3-triazol-4-yl][1,1'-biphenyl]-3-yl]-1-piperidinyl-methanone. CAS Number: 1472640-86-0. Molecular Formula: C32H33N5O2. Formula Weight: 519.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 30 mg/ml. lambdamax: 279 nm. SMILES: O=C(N1N=NC(C2=CC=C(C3=CC=CC(C(N4CCCCC4)=O)=C3)C=C2)=C1)N5C(C6=CC=CC=C6)CCCC5. InChi Code: InChI=1S/C32H33N5O2/c38-31(35-19-6-2-7-20-35)28-13-9-12-27(22-28)24-15-17-25(18-16-24)29-23-37(34-33-29)32(39)36-21-8-5-14-30(36)26-10-3-1-4-11-26/h1,3-4,9-13,15-18,22-23,30H,2,5-8,14,19-21H2. InChi Key: SGQNTNACVSWXMA-UHFFFAOYSA-N.