Details
Stereochemistry | ACHIRAL |
Molecular Formula | C7H9N5S |
Molecular Weight | 195.245 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=S)N\N=C\C1=NC=CC=C1N
InChI
InChIKey=XMYKNCNAZKMVQN-NYYWCZLTSA-N
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+
Triapine (3-aminopyridine-2-carboxaldehyde thiosemcirbazone, (3-AP; NTO-1151; OCX-0191) is a novel small molecule ribonucleotide reductase inhibitor that acts on the M2 (R2) subunit. Ribonucleotide reductase is an enzyme involved in the de novo synthesis of deoxyribonucleotides, which are critical for DNA replication and DNA repair. Triapine has been used in trials phase II studying the treatment of Lung Cancer, Kidney Cancer, Prostate Cancer Pancreatic Cancer, among others. Recently was published the article describing, that the triple combination triapine-cisplatin-paclitaxel was safe and provided a rational basis for a follow-up phase II trial to evaluate the efficacy and progression-free survival in women with metastatic or recurrent uterine cervix cancer.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL3301398 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28421163 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
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no | ||||
no | ||||
yes [Activation 6 uM] | ||||
yes [Inhibition 6 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25749419/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
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major | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
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The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. | 2011 Mar 5 |
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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. | 2014 Oct 1 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17393073
Triapine was given at a schedule of 96 mg/m2 2-h infusion daily x 4 repeated every 2 weeks in patients with recurrent renal cell carcinoma (RCC)
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16675588
For in vitro evaluations, DU145 and U251 cells were exposed to 5 μmol/L and PSN1 to 3 μmol/L Triapine, concentrations that after 16 hours reduced survival by ∼50%. To evaluate the effects of Triapine on tumor cell radiosensitivity when given before irradiation, cultures were exposed to Triapine for 16 hours, irradiated, rinsed, and fed Triapine-free media, colonies were counted 10 to 12 days later and survival curves generated after normalizing for the cytotoxicity induced by Triapine alone. The exposure to Triapine before irradiation resulted in a significant increase in the radiosensitivity of each of the tumor cell lines with dose enhancement factors at a surviving fraction of 0.10 of 1.8, 1.5, and 1.6 for DU145, U251, and PSN1, respectively.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
588817
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NCI_THESAURUS |
C2150
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9571836
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143621-35-6
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236392-56-6
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DB11940
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Triapine
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U4XIL4091C
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C2242
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PRIMARY | NCIT |
ACTIVE MOIETY