3-Aminopyridine-2-carboxaldehyde thiosemicarbazone


3-Aminopyridine-2-carboxaldehyde thiosemicarbazone
Names
IUPAC name
3-aminopyridine-2-carbaldehyde thiosemicarbazone
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.229.703
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PubChem CID
InChI
  • 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
SMILES
  • C1=CC(=C(N=C1)C=NNC(=S)N)N
  • S=C(N\N=C\c1ncccc1N)N
Properties
Chemical formula
 C7H9N5S
Molar mass 195.25 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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.[1]

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

Triapine (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. (www.nanopharmaceutics.com) continue to support clinical studies with the NCI. It has undergone thirty Phase 1 and Phase 2 clinical trials and is currently in four active clinical studies including the Phase 3 clinical trial "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 " ClinicalTrials.gov Identifier: NCT02466971.

References

  1. ↑ 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.
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