Irinotecan(CPT-11)is a cytotoxic drug that has wide applicability and usage in cancer treatment.Despite its success,patients suffer dose-dependent diarrhea,limiting the drugs efficacy.No effective therapy is available for this unmet medical need.As a prodrug,CPT-11 is hydrolyzed by carboxylesterases(CES)in liver to convert to its therapeutically active form SN-38,a potent type I DNA topoisomerase inhibitor.SN-38 undergoes further metabolism in both liver and intestine by UDT-glucuronosyl-transferase(UGT)which conjugates it with glucuronic acid to form the inactive SN-38G.