Triapine, also known as 3-AP and OCX-191, is a synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity. Triapine inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis. This agent has been shown to inhibit tumor growth in vitro.
Chemical Formula: C7H9N5S
Exact Mass: 195.05787
Molecular Weight: 195.24
Elemental Analysis: C, 43.06; H, 4.65; N, 35.87; S, 16.42
InChi Code: 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+
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
AP (Triapine) is a potent derivative of α-heterocyclic carboxaldehyde thiosemicarbazone (HCT) that inhibits hRRM2 and p53R2 isoforms of the M2 subunit.3-AP (Triapine) is thought to inhibit ribonucleotide reductase through its preformed iron chelate, rather than directly by removing iron from the active site. In cells containing less topoisomerase IIα fewer DNA strand breaks will be produced, and thus topoisomerase II poisons will be less inhibitory in the K/VP.5 cell line. The IC50s for Dp44mT growth inhibition are 48±9 nM and 60±12 nM, for K562 and K/VP.5 cells, respectively. The IC50s for 3-AP growth inhibition are 476±39 nM and 661±69 nM for K562 and K/VP.5 cells, respectively. PKIH and DpT Fe chelators show high antiproliferative activity against a range of tumor cell lines. Dp44mT shows the greatest antitumor efficacy with an IC50 that ranged from 0.005 to 0.4 μM. The average IC50 of Dp44mT over 28 cell types is 0.03±0.01 μM, which is significantly lower than that of 3-AP (Triapine; average IC50: 1.41±0.37 μM).
AP (Triapine) causes a significant increase (1.7-fold) in splenic weight when expressed as a percentage of total body weight (1.02±0.06%; n=25) compared with control mice (0.6±0.03%; n=27). In the long-term group, a significant increase in heart weight is observed after Dp44mT (0.4 mg/kg per day) (0.8±0.06%; n=4) compared with control mice (0.5±0.01%; n=6). A significant decrease in the expression of Ndrg1, TfR1, and VEGF1 in the liver is noted for Dp44mT- and 3-AP (12 mg/kg per day)-treated animals. The decreased expression could be related to the increased liver Fe in both Dp44mT- and 3-AP-treated mice.
Ishiguro K, Lin ZP, Penketh PG, Shyam K, Zhu R, Baumann RP, Zhu YL, Sartorelli AC, Rutherford TJ, Ratner ES. Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15. PubMed PMID: 25130544; PubMed Central PMCID: PMC4163625.
Kunos CA, Sherertz TM. Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer. Front Oncol. 2014 Jul 24;4:184. doi: 10.3389/fonc.2014.00184. eCollection 2014. PubMed PMID: 25105092; PubMed Central PMCID: PMC4109518.
Lin ZP, Ratner ES, Whicker ME, Lee Y, Sartorelli AC. Triapine disrupts CtIP-mediated homologous recombination repair and sensitizes ovarian cancer cells to PARP and topoisomerase inhibitors. Mol Cancer Res. 2014 Mar;12(3):381-93. doi: 10.1158/1541-7786.MCR-13-0480. Epub 2014 Jan 10. PubMed PMID: 24413181; PubMed Central PMCID: PMC3962722.
Trondl R, Flocke LS, Kowol CR, Heffeter P, Jungwirth U, Mair GE, Steinborn R, Enyedy Ã‰A, Jakupec MA, Berger W, Keppler BK. Triapine and a more potent dimethyl derivative induce endoplasmic reticulum stress in cancer cells. Mol Pharmacol. 2014 Mar;85(3):451-9. doi: 10.1124/mol.113.090605. Epub 2013 Dec 30. PubMed PMID: 24378333.
Aye Y, Long MJ, Stubbe J. Mechanistic studies of semicarbazone triapine targeting human ribonucleotide reductase in vitro and in mammalian cells: tyrosyl radical quenching not involving reactive oxygen species. J Biol Chem. 2012 Oct 12;287(42):35768-78. doi: 10.1074/jbc.M112.396911. Epub 2012 Aug 22. PubMed PMID: 22915594; PubMed Central PMCID: PMC3471726.
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