CES2

Carboxylesterase 2 (CES2), also known as CES2A or hCE-2, is a serine hydrolase predominantly expressed in the small intestine and liver. It catalyzes the hydrolysis of ester, amide, and thioester bonds, critical for metabolizing xenobiotics and endogenous lipids. Notably, it inactivates SN-38, the active metabolite of irinotecan, a first-line chemotherapeutic for colorectal cancer.
CES2 participates in drug metabolism pathways and interacts with cytochrome P450 enzymes to regulate drug efficacy and toxicity. Dysregulated CES2 activity correlates with reduced irinotecan response and heightened gastrointestinal side effects. Ongoing research targets CES2 inhibitors to boost irinotecan’s anticancer effects while alleviating adverse reactions, with several small-molecule candidates in preclinical development.