3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, also called Triapine) is a substance that is being studied in the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. It belongs to the family of drugs called

ribonucleotide reductase inhibitor Ribonucleotide reductase inhibitors are a family of anti-cancer drugs that interfere with the growth of tumor cells by blocking the formation of deoxyribonucleotides (building blocks of DNA). Examples include: * motexafin gadolinium. * hydroxyurea ...

s. 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 the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occur ...

. DNA synthesis is required for cellular proliferation and

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

. 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 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. Vion Pharmaceuticals has also filed several use patents concerning the antiviral and antifungal activity of 3AP. 3AP was initially developed by

Vion Pharmaceuticals Vion Pharmaceuticals, Inc. was a New Haven, Connecticut based pharmaceutical company founded in March 1992 to commercialize several discoveries made in the biomedical laboratories at Yale University. Clinical development Two anticancer agents, On ...

until company declared bankruptcy in December 2009. Nanotherapeutics, Inc. acquired the product from bankruptcy in 2010 and supported trials at NCI until 2018 when the product was transferred to Nanoshift, LLC. Nanoshift LLC and Nanopharmaceutics, Inc. continue to support clinical studies with the NCI.

References

External links

NCT02466971 Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers

NCT02595879 Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal CancerNCT04234568 Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors

NCT04494113 Testing the Response to the Anti-cancer Drug, Triapine, in Uterine Cancers Using Markers From the Tissue at the Time of Hysterectomy
{{DEFAULTSORT:Aminopyridine-2-carboxaldehyde thiosemicarbazone, 3- Experimental cancer drugs Thiosemicarbazone Aminopyridines