KLH45

KLH45 is an inhibitor of the phospholipase DDHD domain containing 2 (DDHD2; IC50 = 1.3 nM). It is selective for DDHD2 over greater than 50 serine hydrolases, including DDHD1 and Sec23ip, but does inhibit α/β-hydrolase domain-containing protein 6 (ABHD6). It inhibits DDHD2 and ABHD6 in Neuro2A cells when used at a concentration of less than 10 nM and inhibits DDHD2 by greater than 95% at a concentration of 25 nM. KLH45 (2 µM) prevents increases in triacylglycerol (TAG) hydrolase activity in HEK293T cell lysates expressing recombinant DDHD2 and incubated with a radiolabeled TAG substrate. It decreases TAG levels in the CNS of mice when administered at a dose of 20 mg/kg twice per day for four days. KLH45 (2 µM) also reverses DDHD2-induced lipid droplet reduction in COS-7 cells expressing recombinant DDHD2 and loaded with oleic acid.