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  • A synthetic, highly lipophilic derivative of camptothecin, with potential antineoplastic and radiosensitizing activities. Silatecan DB-67 binds to and stabilizes the topoisomerase I-DNA covalent complex, inhibiting the religation of topoisomerase I-mediated single-stranded DNA breaks and producing lethal double-stranded DNA breaks when encountered by the DNA replication machinery; inhibition of DNA replication and apoptosis follow. Camptothecin readily undergoes hydrolysis at physiological pH, changing its conformation from the active lactone structure to an inactive carboxylate form. Modifications on the E ring of camptothecin prevent binding of human serum albumin, which prefers the inactive carboxylate form, thereby enhancing the stability of the active lactone structure and resulting in prolonged agent activity. In addition, this agent may radiosensitize tumor cells. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C64618\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C64618\' NCI Thesaurus)
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