Prodrugs and ADC Derivatives of Non-Camptothecin TOP1-Targeting Cancer Chemotherapeutics

Edmond LaVoie (Inventor), Ajit Parhi (Inventor)

Research output: Innnovationinnovation


Schematic Structure of an Antibody-Drug Conjugate (ADC) ( Invention Summary: Topoisomerase 1 (Top1) is an essential enzyme in mammalian cells and is a validated target for the treatment of human cancers. Topotecan and irinotecan (camptothecin analogues) are two FDA approved Top1-targeted drugs. Despite being powerful anticancer drugs, camptothecin derivatives exhibit clinical limitations due to the instability of their α-hydroxylactone six-membered E-ring structure. Genz-644282 is a novel non-camptothecin topoisomerase I inhibitor developed by Rutgers scientists. Genz-644282 has consistently exhibited cytotoxicity against human tumor cell at IC50 concentrations at or below 1.0 nM.  Unlike camptothecin based topoisomerase I targeting agents, Genz-644282 has been shown not to be a substrate for efflux transporters associated with multidrug resistance as observed in human tumors. Studies in tumor-bearing laboratory animals have demonstrated that Genz-644282 is approximately 20-fold more potent as an antitumor agent than irinotecan. An Investigational New Drug (IND) application has been approved by the FDA and a Phase I study for Genz-644282 has been completed. New technology developed at Ernest Mario School of Pharmacy is related to specific prodrug derivatives of Genz-644282 and their antibody drug conjugates (with self-immolative linkers) that will further increase tumor specificity. The advantage of this technology is that the active principal of the antibody drug conjugate is already well established. And Phase I study with the “active pharmaceutical ingredient” (API) of these prodrugs or the war-head of the ADC has been completed. Market Applications: Chemotherapy Oncology Cancer Treatment Advantages: Targeted delivery. IND application has been approved by FDA for the parent compound (Genz-644282) of these pro-drugs. Phase I clinical trial has been completed for the parent compound (Genz-644282). I ntellectual Property & Development Status: Multiple patent applications pending. Available for licensing and/or for research collaboration.
Original languageEnglish (US)
StatePublished - Mar 2019


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