View source for Triapine

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| IUPAC_name        = <nowiki>[(E)-(3-aminopyridin-2-yl)methylideneamino]thiourea</nowiki>
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'''Triapine''' (also known as '''3-aminopyridine-2-carboxaldehyde thiosemicarbazone''' or '''3-AP''') is an [[investigational drug]] that is being evaluated 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.<ref>{{cite journal | vauthors = Kowol CR, Trondl R, Heffeter P, Arion VB, Jakupec MA, Roller A, Galanski MS, Berger W, Keppler BK | title = Impact of Metal Coordination on Cytotoxicity of 3-Aminopyridine-2-carboxaldehyde Thiosemicarbazone (Triapine) and Novel Insights into Terminal Dimethylation | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 16 | pages = 5032–5043 | date = 2009 | pmid = 19637923 | doi = 10.1021/jm900528d }}</ref>

It belongs to the family of drugs called [[ribonucleotide reductase inhibitor]]s.<ref name="Alvarado_2002">{{cite journal | vauthors = Alvarado Y, Giles FJ, Tsimberidou AM | title = Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies | journal = Expert Review of Anticancer Therapy | volume = 2 | issue = 4 | pages = 437–448 | date = August 2002 | pmid = 12647987 | doi = 10.1586/14737140.2.4.437 | s2cid = 30047759 | url = http://www.future-drugs.com/doi/abs/10.1586/14737140.2.4.437?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov | url-access = subscription }}</ref>

== Pharmacology ==

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.

It has also been reported to have [[neuroprotective]] properties.<ref>{{cite journal | vauthors = Jiang ZG, Lebowitz MS, Ghanbari HA | title = Neuroprotective activity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811), a cancer therapeutic agent | journal = CNS Drug Reviews | volume = 12 | issue = 1 | pages = 77–90 | date = March 2006 | pmid = 16834759 | doi = 10.1111/j.1527-3458.2006.00077.x | pmc = 6741723 }}</ref>


== Development ==

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==
{{reflist}}

==External links==
* {{ClinicalTrialsGov|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}}
* {{ClinicalTrialsGov|NCT02595879|Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal Cancer}}
* {{ClinicalTrialsGov|NCT02466971|Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors}}
* {{ClinicalTrialsGov|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-}}
[[Category:Experimental cancer drugs]]
[[Category:3-Aminopyridines]]
[[Category:Thiosemicarbazones]]