WWL229 is a highly selective inhibitor of mouse Carboxylesterase 3 (Ces3) and human CES1 (orthologue of mCes3), serine hydrolases involved in lipolysis in addition to their activities as liver detoxification enzymes. WWL229 inhibits mCes3 with an IC50 of 10 μM, but not Ces1f, ABHD6 or other tested serine hydrolases. In a recent study, hCES1 activity was found to be increased two-fold in obese individuals and patients with type 2 diabetes compared to lean subjects, and is thought to generate surplus fatty acids th at can deposit ectopically in tissues. WWL229 inhibits adipocyte basal lipolysis and promotes differentiation and lipid storage in adipocytes.
