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WWL229 is a selective, covalent **inhibitor of carboxylesterase enzymes**, specifically mouse Carboxylesterase 3 (Ces3), the human ortholog carboxylesterase 1 (CES1), and mouse Ces1d, all part of the serine hydrolase family. These enzymes are involved in hepatic detoxification and lipid metabolism, including the regulation of lipolysis and triglyceride storage. WWL229 inhibits mouse Ces3 with an IC50 of 10 μM and shows high specificity, not affecting related enzymes such as Ces1f or ABHD6. By blocking CES1/Ces3, WWL229 inhibits basal lipolysis in adipocytes, increases differentiation and lipid storage, induces triglyceride accumulation, reduces free fatty acid levels, slows de novo lipogenesis, and alters the dynamics of lipid droplet formation. It has been used in research to probe lipid metabolism, adipocyte function, liver metabolism, thermogenesis, and tumor biology. In vivo, WWL229 can sensitize hepatocellular carcinoma (HCC) cells to cisplatin and alters the response to inflammation by augmenting lung inflammation in a sex-specific manner. WWL229 is strictly for research use and is not approved for human or clinical use[1][2][3][4][5].
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