Triapine
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MedKoo CAT#: 203000

CAS#: 143621-35-6

Description: 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.


Price and Availability

Size
Price

1g
USD 2950
Size
Price

2g
USD 3950
Size
Price

5g
USD 5950

Triapine, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: from $30.00 (USA); from $45.00 (Canada); from $70.00 (international).


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 203000
Name: Triapine
CAS#: 143621-35-6
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


Related CAS #: 143621-35-6   236392-56-6  

Synonym: 3AP; 3AP; 3Apct; OCX 191; OCX191; OCX191; AIDS179996; AIDS179996; NSC663249. PAN-811; PAN811; PAN 811; Triapine

IUPAC/Chemical Name: (E)-2-((3-aminopyridin-2-yl)methylene)hydrazinecarbothioamide

InChi Key: XMYKNCNAZKMVQN-NYYWCZLTSA-N

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+

SMILES Code: NC1=CC=CN=C1/C=N/NC(N)=S


Technical Data

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).

Harmonized System Code:
293490


Additional Information

 
Triapine is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called ribonucleotide reductase inhibitors.  Triapine  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 Triapine iron chelate is redox active and there have been several reports in the literature ascribing this property to some of the biological activities of Triapine.   (source: http://en.wikipedia.org/wiki/3-Aminopyridine-2-carboxaldehyde_thiosemicarbazone).
Triapine is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called ribonucleotide reductase inhibitors. 
Triapine
 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
iron chelate is redox active and there have been several reports in the literature ascribing this property to some of the biological activities of
Triapine
.
 
(source: http://en.wikipedia.org/wiki/3-Aminopyridine-2-carboxaldehyde_thiosemicarbazone).
  
Ac cording to Wikipedia.com, Triapine  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. Triapine  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. As of 2006, Triapine  is being developed by Vion Pharmaceuticals. It has undergone Phase 1 and Phase 2 clinical trials. Vion Pharmaceuticals has also filed several use patents concerning the antiviral and antifungal activity of Triapine. (source: http://en.wikipedia.org/wiki/3-Aminopyridine-2-carboxaldehyde_thiosemicarbazone).
cording to Wikipedia.com, Triapine
 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.
Triapine
 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. As of 2006,
Triapine
 is being developed by Vion Pharmaceuticals. It has undergone Phase 1 and Phase 2 clinical trials. Vion Pharmaceuticals has also filed several use patents concerning the antiviral and antifungal activity of
Triapine. (source: http://en.wikipedia.org/wiki/3-Aminopyridine-2-carboxaldehyde_thiosemicarbazone).
 
 


References

 1: 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.

2: 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.

3: 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.

4: Trondl R, Flocke LS, Kowol CR, Heffeter P, Jungwirth U, Mair GE, Steinborn R, Enyedy ÉA, 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.

5: 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.

6: Chitambar CR, Antholine WE. Iron-targeting antitumor activity of gallium compounds and novel insights into triapine(®)-metal complexes. Antioxid Redox Signal. 2013 Mar 10;18(8):956-72. doi: 10.1089/ars.2012.4880. Epub 2012 Oct 3. Review. PubMed PMID: 22900955; PubMed Central PMCID: PMC3557436.

7: Mortazavi A, Ling Y, Martin LK, Wei L, Phelps MA, Liu Z, Harper EJ, Ivy SP, Wu X, Zhou BS, Liu X, Deam D, Monk JP, Hicks WJ, Yen Y, Otterson GA, Grever MR, Bekaii-Saab T. A phase I study of prolonged infusion of triapine in combination with fixed dose rate gemcitabine in patients with advanced solid tumors. Invest New Drugs. 2013 Jun;31(3):685-95. doi: 10.1007/s10637-012-9863-1. Epub 2012 Jul 31. PubMed PMID: 22847785; PubMed Central PMCID: PMC3646991.

8: Martin LK, Grecula J, Jia G, Wei L, Yang X, Otterson GA, Wu X, Harper E, Kefauver C, Zhou BS, Yen Y, Bloomston M, Knopp M, Ivy SP, Grever M, Bekaii-Saab T. A dose escalation and pharmacodynamic study of triapine and radiation in patients with locally advanced pancreas cancer. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e475-81. doi: 10.1016/j.ijrobp.2012.06.003. Epub 2012 Jul 17. PubMed PMID: 22818416; PubMed Central PMCID: PMC3477302.

9: Quach P, Gutierrez E, Basha MT, Kalinowski DS, Sharpe PC, Lovejoy DB, Bernhardt PV, Jansson PJ, Richardson DR. Methemoglobin formation by triapine, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), and other anticancer thiosemicarbazones: identification of novel thiosemicarbazones and therapeutics that prevent this effect. Mol Pharmacol. 2012 Jul;82(1):105-14. doi: 10.1124/mol.112.078964. Epub 2012 Apr 16. PubMed PMID: 22508546.

10: Yalowich JC, Wu X, Zhang R, Kanagasabai R, Hornbaker M, Hasinoff BB. The anticancer thiosemicarbazones Dp44mT and triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIα. Biochem Pharmacol. 2012 Jul 1;84(1):52-8. doi: 10.1016/j.bcp.2012.03.021. Epub 2012 Apr 4. PubMed PMID: 22503743; PubMed Central PMCID: PMC3348365.

11: Popović-Bijelić A, Kowol CR, Lind ME, Luo J, Himo F, Enyedy EA, Arion VB, Gräslund A. Ribonucleotide reductase inhibition by metal complexes of Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone): a combined experimental and theoretical study. J Inorg Biochem. 2011 Nov;105(11):1422-31. doi: 10.1016/j.jinorgbio.2011.07.003. Epub 2011 Jul 31. PubMed PMID: 21955844; PubMed Central PMCID: PMC3374975.

12: Enyedy ÉA, Primik MF, Kowol CR, Arion VB, Kiss T, Keppler BK. Interaction of Triapine and related thiosemicarbazones with iron(III)/(II) and gallium(III): a comparative solution equilibrium study. Dalton Trans. 2011 Jun 14;40(22):5895-905. doi: 10.1039/c0dt01835j. Epub 2011 Apr 27. PubMed PMID: 21523301; PubMed Central PMCID: PMC3372890.

13: Myers JM, Antholine WE, Zielonka J, Myers CR. The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. Toxicol Lett. 2011 Mar 5;201(2):130-6. doi: 10.1016/j.toxlet.2010.12.017. Epub 2010 Dec 31. PubMed PMID: 21195754.

14: Kolesar J, Brundage RC, Pomplun M, Alberti D, Holen K, Traynor A, Ivy P, Wilding G. Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine®) in cancer patients. Cancer Chemother Pharmacol. 2011 Feb;67(2):393-400. doi: 10.1007/s00280-010-1331-z. Epub 2010 May 4. PubMed PMID: 20440618; PubMed Central PMCID: PMC3059107.

15: Kowol CR, Trondl R, Arion VB, Jakupec MA, Lichtscheidl I, Keppler BK. Fluorescence properties and cellular distribution of the investigational anticancer drug triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) and its zinc(II) complex. Dalton Trans. 2010 Jan 21;39(3):704-6. doi: 10.1039/b919119b. Epub 2009 Oct 22. PubMed PMID: 20066211.

16: Kowol CR, Trondl R, Heffeter P, Arion VB, Jakupec MA, Roller A, Galanski M, Berger W, Keppler BK. Impact of metal coordination on cytotoxicity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (triapine) and novel insights into terminal dimethylation. J Med Chem. 2009 Aug 27;52(16):5032-43. doi: 10.1021/jm900528d. PubMed PMID: 19637923.

17: Nutting CM, van Herpen CM, Miah AB, Bhide SA, Machiels JP, Buter J, Kelly C, de Raucourt D, Harrington KJ. Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2009 Jul;20(7):1275-9. doi: 10.1093/annonc/mdn775. Epub 2009 Feb 26. PubMed PMID: 19246715.

18: Traynor AM, Lee JW, Bayer GK, Tate JM, Thomas SP, Mazurczak M, Graham DL, Kolesar JM, Schiller JH. A phase II trial of triapine (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Study 1503. Invest New Drugs. 2010 Feb;28(1):91-7. doi: 10.1007/s10637-009-9230-z. Epub 2009 Feb 24. PubMed PMID: 19238328; PubMed Central PMCID: PMC3045859.

19: Schelman WR, Morgan-Meadows S, Marnocha R, Lee F, Eickhoff J, Huang W, Pomplun M, Jiang Z, Alberti D, Kolesar JM, Ivy P, Wilding G, Traynor AM. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2009 May;63(6):1147-56. doi: 10.1007/s00280-008-0890-8. Epub 2008 Dec 13. PubMed PMID: 19082825; PubMed Central PMCID: PMC3050713.

20: Kolesar JM, Schelman WR, Geiger PG, Holen KD, Traynor AM, Alberti DB, Thomas JP, Chitambar CR, Wilding G, Antholine WE. Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine. J Inorg Biochem. 2008 Apr;102(4):693-8. Epub 2007 Oct 30. PubMed PMID: 18061679; PubMed Central PMCID: PMC2390869.

21: Ma B, Goh BC, Tan EH, Lam KC, Soo R, Leong SS, Wang LZ, Mo F, Chan AT, Zee B, Mok T. A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells. Invest New Drugs. 2008 Apr;26(2):169-73. Epub 2007 Sep 12. PubMed PMID: 17851637.

22: Karp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leuk Res. 2008 Jan;32(1):71-7. Epub 2007 Jul 20. PubMed PMID: 17640728; PubMed Central PMCID: PMC2726775.

23: Knox JJ, Hotte SJ, Kollmannsberger C, Winquist E, Fisher B, Eisenhauer EA. Phase II study of Triapine in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161). Invest New Drugs. 2007 Oct;25(5):471-7. Epub 2007 Mar 28. PubMed PMID: 17393073.

24: Gojo I, Tidwell ML, Greer J, Takebe N, Seiter K, Pochron MF, Johnson B, Sznol M, Karp JE. Phase I and pharmacokinetic study of Triapine, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies. Leuk Res. 2007 Sep;31(9):1165-73. Epub 2007 Feb 26. PubMed PMID: 17324462.

25: Sigmond J, Kamphuis JA, Laan AC, Hoebe EK, Bergman AM, Peters GJ. The synergistic interaction of gemcitabine and cytosine arabinoside with the ribonucleotide reductase inhibitor triapine is schedule dependent. Biochem Pharmacol. 2007 May 15;73(10):1548-57. Epub 2007 Jan 21. PubMed PMID: 17324380.

26: Yu Y, Wong J, Lovejoy DB, Kalinowski DS, Richardson DR. Chelators at the cancer coalface: desferrioxamine to Triapine and beyond. Clin Cancer Res. 2006 Dec 1;12(23):6876-83. Review. PubMed PMID: 17145804.

27: Barker CA, Burgan WE, Carter DJ, Cerna D, Gius D, Hollingshead MG, Camphausen K, Tofilon PJ. In vitro and in vivo radiosensitization induced by the ribonucleotide reductase inhibitor Triapine (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone). Clin Cancer Res. 2006 May 1;12(9):2912-8. PubMed PMID: 16675588.

28: Shao J, Zhou B, Di Bilio AJ, Zhu L, Wang T, Qi C, Shih J, Yen Y. A Ferrous-Triapine complex mediates formation of reactive oxygen species that inactivate human ribonucleotide reductase. Mol Cancer Ther. 2006 Mar;5(3):586-92. PubMed PMID: 16546972.

29: Foltz LM, Dalal BI, Wadsworth LD, Broady R, Chi K, Eisenhauer E, Kobayashi K, Kollmannsburger C. Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. Am J Hematol. 2006 Mar;81(3):210-1. PubMed PMID: 16493607.

30: Yee KW, Cortes J, Ferrajoli A, Garcia-Manero G, Verstovsek S, Wierda W, Thomas D, Faderl S, King I, O'brien SM, Jeha S, Andreeff M, Cahill A, Sznol M, Giles FJ. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leuk Res. 2006 Jul;30(7):813-22. Epub 2006 Feb 14. PubMed PMID: 16478631.

31: Alvero AB, Chen W, Sartorelli AC, Schwartz P, Rutherford T, Mor G. Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) induces apoptosis in ovarian cancer cells. J Soc Gynecol Investig. 2006 Feb;13(2):145-52. PubMed PMID: 16443509.

32: Schoenfeldt M. Clinical trials referral resource. Current clinical trials investigating Triapine. Oncology (Williston Park). 2004 Aug;18(9):1147, 1149-50. PubMed PMID: 15471198.

33: Murren J, Modiano M, Clairmont C, Lambert P, Savaraj N, Doyle T, Sznol M. Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors. Clin Cancer Res. 2003 Sep 15;9(11):4092-100. PubMed PMID: 14519631.

34: Giles FJ, Fracasso PM, Kantarjian HM, Cortes JE, Brown RA, Verstovsek S, Alvarado Y, Thomas DA, Faderl S, Garcia-Manero G, Wright LP, Samson T, Cahill A, Lambert P, Plunkett W, Sznol M, DiPersio JF, Gandhi V. Phase I and pharmacodynamic study of Triapine, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia. Leuk Res. 2003 Dec;27(12):1077-83. PubMed PMID: 12921943.

35: Chaston TB, Lovejoy DB, Watts RN, Richardson DR. Examination of the antiproliferative activity of iron chelators: multiple cellular targets and the different mechanism of action of triapine compared with desferrioxamine and the potent pyridoxal isonicotinoyl hydrazone analogue 311. Clin Cancer Res. 2003 Jan;9(1):402-14. PubMed PMID: 12538494.

36: Finch RA, Liu M, Grill SP, Rose WC, Loomis R, Vasquez KM, Cheng Y, Sartorelli AC. Triapine (3-aminopyridine-2-carboxaldehyde- thiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem Pharmacol. 2000 Apr 15;59(8):983-91. PubMed PMID: 10692563.

37: Finch RA, Liu MC, Cory AH, Cory JG, Sartorelli AC. Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 3-AP): an inhibitor of ribonucleotide reductase with antineoplastic activity. Adv Enzyme Regul. 1999;39:3-12. Review. PubMed PMID: 10470363.