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3-Aminopyridine-2-carboxaldehyde thiosemicarbazone

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3-Aminopyridine-2-carboxaldehyde thiosemicarbazone
Names
IUPAC name
3-aminopyridine-2-carbaldehyde thiosemicarbazone
Other names
3AP, Triapine, OCX-0191
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.229.703 Edit this at Wikidata
UNII
  • InChI=1S/C7H9N5S/c8-5-2-1-3-10-6(5)4-11-12-7(9)13/h1-4H,8H2,(H3,9,12,13)/b11-4+ checkY
    Key: XMYKNCNAZKMVQN-NYYWCZLTSA-N checkY
  • InChI=1/C7H9N5S/c8-5-2-1-3-10-6(5)4-11-12-7(9)13/h1-4H,8H2,(H3,9,12,13)/b11-4+
    Key: XMYKNCNAZKMVQN-NYYWCZLTBO
  • C1=CC(=C(N=C1)C=NNC(=S)N)N
  • S=C(N\N=C\c1ncccc1N)N
Properties
C7H9N5S
Molar mass 195.24 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, also called Triapine) is substance of interest for the treatment of cancer. It is a thiosemicarbazone derivative of 3-aminopyridine-2-carboxaldehyde. It presents an N-N-S array of donor sites that strongly bind iron, robbing iron-containing enzymes of their prosthetic group.[1]

It belongs to the family of drugs called ribonucleotide reductase inhibitors.[2]

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 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 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

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  1. ^ Kowol, Christian R.; Trondl, Robert; Heffeter, Petra; Arion, Vladimir B.; Jakupec, Michael A.; Roller, Alexander; Galanski, Mathea Sophia; Berger, Walter; Keppler, Bernhard K. (2009). "Impact of Metal Coordination on Cytotoxicity of 3-Aminopyridine-2-carboxaldehyde Thiosemicarbazone (Triapine) and Novel Insights into Terminal Dimethylation". Journal of Medicinal Chemistry. 52 (16): 5032–5043. doi:10.1021/jm900528d. PMID 19637923.
  2. ^ Tsimberidou AM; Alvarado Y; Giles FJ (August 2002). "Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies". Expert Rev Anticancer Ther. 2 (4): 437–48. doi:10.1586/14737140.2.4.437. PMID 12647987. S2CID 30047759.
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