Monoacylglycerol O-acyltransferase 3 (MOGAT3)

Monoacylglycerol O-acyltransferase 3 (MOGAT3) is an enzyme that catalyzes the conversion of 2-monoacylglycerol and fatty acyl-CoA into diacylglycerol, a key intermediate in triglyceride biosynthesis[5]. It is primarily involved in lipid metabolic pathways, especially in the liver, and plays a role in regulating lipid storage, cellular energy balance, and metabolic disorders such as nonalcoholic fatty liver disease and insulin resistance[3][5]. Pathologically, MOGAT3 has recently been identified as a driver of acquired resistance to anti-BRAF/EGFR therapies in BRAF V600E-mutant colorectal cancer through promotion of diacylglycerol (DAG) accumulation, which reactivates MAPK signaling and contributes to tumor cell survival[1][2]. Small-molecule inhibition of MOGAT3 or reduction of DAG can restore therapeutic sensitivity in resistant models with minimal toxicity observed in preclinical studies[2].

Other names

2-acylglycerol O-acyltransferase 3DC7DGAT2L7UNQ9383/PRO34208MGAT3hDC7DGAT2L2Acyl-CoA:monoacylglycerol acyltransferase 3Diacylglycerol O-acyltransferase candidate 7Diacylglycerol acyltransferase 2-like protein 7

Inhibitors reduce intratumoral diacylglycerol accumulation by blocking DAG synthesis; co-administration with BRAF/EGFR inhibitors restores drug sensitivity by blocking MAPK pathway reactivation in resistant cancer[2].