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==Overview==
==Overview==
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Latest revision as of 18:58, 8 August 2012

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Overview

3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, also called Triapine) is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called ribonucleotide reductase inhibitors. 3AP is a potent inhibitor of ribonucleotide reductase, the rate determining enzyme in the supply of deoxynucleotides (DNA building blocks) for DNA synthesis. DNA synthesis is required for cellular proliferation and DNA repair. It is therefore not surprising that it has broad spectrum antitumor activity and synergizes with antitumor drugs that target DNA. It is a very strong iron chelator and in the body it is likely that the iron chelate is the active species that quenches the active site tyrosyl radical required by ribonucleotide reductase for its enzymatic activity. The 3AP iron chelate is redox active and there have been several reports in the literature ascribing this property to some of the biological activities of 3AP. 3AP is a product of the laboratory of Dr Alan C. Sartorelli, a renowned cancer researcher in the Yale University School of Medicine Pharmacology Department. Dr. Sartorelli has a long standing interest in ribonucleotide reductase inhibitors as anticancer agents, and in collaboration with the late Dr. Tai-Shun Lin, and Dr. Mao-Chin Liu, a large number of thiosemicarbazone based ribonucleotide reductase inhibitors were synthesized over several decades. 3AP was chosen, based on the results of studying and the screening these products, as the candidate inhibitor most likely to express activity in the setting of human neoplastic disease. As of 2006, 3AP is being developed by Vion Pharmaceuticals. It has undergone Phase 1 and Phase 2 clinical trials. Vion Pharmaceuticals has also filed several use patents concerning the antiviral and antifungal activity of 3AP.

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