KT-185 (KT185) is a potent, selective, irreversible and orally-active α/β-hydrolase domain 6 (ABHD6) inhibitor with IC50 of 0.21 nM.
KT-185 inhibits ABHD6 in a 2-arachidonoyl glycerol (2-AG) hydrolysis assay (IC50=13.6 nM for the mouse recombinant enzyme expressed in HEK293T cells).
KT185 is selective for ABHD6 over diacylglycerol lipase β (DAGLβ) at 1 µM, but inhibits lysophospholipase 1 (LYPLA1) and LYPLA2 at 10 µM.
KT185 (5-10 mg/kg) inhibits ABHD6 activity in mouse liver and brain in vivo.
KT185 inhibits increases in the frequency of spontaneous inhibitory post-synaptic currents (sIPSCs) induced by nicotine in the rat ventral tegmental area (VTA) but does not reduce nicotine self-administration in rats.
