DO53

DO53 is a serine hydrolase inhibitor that targets ABHD6, PAFAH2, PLA2G7, ABHD2 and CES1C. DO53 reduces LPS (HY-D1056A1)-induced cytokine production in the mouse brain, decreases fasting-induced refeeding behavior, and induces hypoactivity in mice. As a DAGL negative control, DO53 shows no activity against DAGLα/β in vivo, and does not affect brain lipid levels, DSE/DSI synaptic plasticity or LPS-induced anhidrosis in mice. DO53 can be used in studies related to LPS-induced neuroinflammation and fasting-induced refeeding^[1][2]. In Vitro:DO53 shows minimal inhibition of recombinant human DAGLα and mouse DAGLβ in membrane lysates from transfected HEK293T cells, with ~100-fold lower activity than DH376 and DO34^[1].
DO53 inhibits carboxylesterase activity in mouse liver membrane proteome, representing a shared off-target with active triazole urea DAGL inhibitors^[2]. In Vivo:DO53 (3-50 mg/kg; i.p.; single dose) does not inhibit brain DAGLα or DAGLβ activity in male C57BL/6 mice at doses up to 50 mg/kg, but does inhibit the off-target serine hydrolases ABHD6 and PLA2G7^[1].
DO53 (50 mg/kg; i.p.; single dose; administered 60-90 minutes prior to LPS treatment) does not modulate LPS-induced brain lipid changes or anapyrexia in male C57BL/6 mice, but does attenuate LPS-induced brain IL-1β production^[1].
DO53 (50 mg/kg; i.p.; single dose) significantly reduces fasting-induced refeeding and hypolocomotes mice, indicating effects on energy balance and locomotion independent of DAGL inhibition^[2].