Case Study: Irinotecan (CPT-11), A Water-soluble Prodrug of SN-38
Irinotecan (CPT-11) is a potent anticancer agent approved for use in the treatment of advanced colorectal cancer, as either a first-line therapy in combination with 5-fluorouracil or in the treatment of 5-flurouracil refractory cases (Sawada et al., 1995; Saltz, 1997). Irinotecan is a prodrug designed to deliver the poorly soluble parent molecule SN-38, an analog of a highly potent plant alkaloid camptothecin (CPT). Camptothecin and its analogs inhibit the nuclear enzyme topoisomerase I, inhibiting replication and demonstrating antitumor activity as an S-phase-specific drug (Garcia-Carbonero and Supko, 2002). The structure and enzymatic bioconversion of CPT-11 to SN-38 is shown in Scheme 1.
KeywordsLactone Form Carboxylate Form Camptothecin Derivative Limited Sampling Model Irinotecan Hydrochloride
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