Irinotecan hydrochloride (CPT-11): A Water Soluble Topoisomerase-I Inhibitor with Enhanced Activity
Irinotecan hydrochloride (CPT-11) is a derivative of 7-ethylcamptothecin (SN-22) [
E0781] or Camptothecin (CPT) [
C1495]. Irinotecan hydrochloride has greater water solubility and enhanced topoisomerase-I inhibitory activity than theirs. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) [
E0748] by a carboxylesterase-converting enzyme. Camptotecin and its derivatives interfere with DNA synthesis by inhibiting the enzyme topoisomerase-I. In order to prevent and correct of topological problems caused by the DNA double helix, topoisomerase-I catalyzes the relaxation of negatively supercoiled DNA, the knotting and unknotting DNA and the linking complementary rings of single-stranded DNA into double-stranded rings. Then the inhibition action induces breaks in single strand DNA. Eventually, this leads to double-strand DNA breaks and apoptosis or cell death. (The product is for research purpose only.)