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Purity: ≥98%
Triapine (formerly NSC-663249;AIDS-179996;AP;OCX191;PAN-811;OCX-191;3AP;NSC663249;PAN811; 3-AP; PAN 811)is a so-called ribonucleotide reductase inhibitor being investigated for cancer treatment. It has a wide range of anticancer properties and is also a strong radiosensitizer and an inhibitor of DNA synthesis. In vitro, tripine M109 lung carcinoma and human A2780 ovarian carcinoma are two cancer cell lines that exhibit strong anti-proliferative activity in response to tripine. Furthermore, Triapine exhibits strong in vivo antitumor efficacy against human A2780 ovarian carcinoma xenograft mice and M109 lung carcinoma.
| Targets |
Ribonucleotide reductase (RR)
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|---|---|
| ln Vitro |
In vitro activity :Triapine (3-AP; PAN-811) is a potent derivative of α-heterocyclic carboxaldehyde thiosemicarbazone (HCT) that inhibits the M2 subunit's hRRM2 and p53R2 isoforms[1]. Instead of directly removing iron from the active site, triapine (3-AP; PAN-811) is thought to inhibit ribonucleotide reductase through its preformed iron chelate. Less DNA strand breaks will be generated in cells with lower levels of topoisomerase IIα, which means that topoisomerase II poisons will have less of an inhibitory effect on the K/VP.5 cell line. For K562 and K/VP.5 cells, the Dp44mT growth inhibition IC50s are 48±9 nM and 60±12 nM, respectively. Triapine growth inhibition IC50 values for K562 and K/VP.5 cells are 476±39 nM and 661±69 nM, respectively[2]. When applied to various tumor cell lines, PKIH and DpT Fe chelators exhibit strong antiproliferative activity. With an IC50 ranging from 0.005 to 0.4 μM, Dp44mT exhibits the highest antitumor efficaciousness. The mean inhibitory concentration (IC50) of Dp44mT across 28 cell types is 0.03±0.01 μM, a considerably smaller value than that of Triapine (3-AP; PAN-811); average IC50: 1.41±0.37 μM)[3].
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| ln Vivo |
Triapine (3-AP; PAN-811) produces a significant increase (1.7-fold) in splenic weight (1.02±0.06%; n = 25) as a percentage of total body weight as compared to control mice (0.6±0.03%; n = 27). In comparison to control mice (0.5±0.01%; n=6), there is a notable increase in heart weight in the long-term group (0.8±0.06%; n=4) following Dp44mT (0.4 mg/kg per day). In animals treated with Dp44mT and Triapine (12 mg/kg per day), there is a noticeable reduction in the expression of Ndrg1, TfR1, and VEGF1 in the liver. The higher liver Fe in both Dp44mT- and triapine-treated mice may be connected to the decreased expression[3].
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| Enzyme Assay |
Dowex 1-borate ion-exchange chromatography is used to assay CDP reductase. Within a final volume of 0.02 mL, the assay mixture includes 10 μL of cellular extract, 3 mM dithiothreitol, 6 mM MgCl2, 30 mM HEPES, 5 mM ATP, and 0.02 μCi of [14C]CDP (52.9 mCi/mmol). The reaction is linear during the 60-minute incubation period.
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| Cell Assay |
The MTT assay is utilized to measure the inhibition of CHO cell growth. K/VP and K562 cells from human leukemia. Five cells, a sub-line derived from K562 that is 26 times more resistant to etoposide and has lower levels of topoisomerase IIα mRNA and protein, are cultured in suspension in MEM with 10% fetal calf serum (FCS). K562 and K/VP for growth inhibition assays. A model ZBF Coulter counter is used to count the cells after 5 cells are plated at a concentration of 1.5×105 cell/mL and incubated for 5 days at different concentrations of Dp44mT, Triapine, or vehicle (DMSO) for 48 hours. Every cell line's IC50 growth inhibitory concentration is determined by fitting a non-linear least-squares model to a two-parameter logistic equation[2].
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| Animal Protocol |
Mice: The mice used are 8–10 week old female BALB/c nu/nu mice. A total of 107 tumor cells that are grown in culture are taken out, suspended in Matrigel, and subcutaneously injected into the right flanks of mice. Tumor size is determined using Vernier calipers following engraftment. It is calculated how much a tumor weighs in cubic millimeters. IV therapy started on day 0 when tumor volumes reached 120 mm3. A solution of 15% propylene glycol in 0.9% saline is used to dissolve chelators, such as triapine, which are then injected intravenously five days a week for a maximum of seven weeks. The vehicle is administered solely to the control mice.
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| References |
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| Additional Infomation |
Triapine 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.
Triapine has been used in trials studying the treatment of Leukemia, Lung Cancer, Kidney Cancer, Prostate Cancer, and Pancreatic Cancer, among others. Triapine 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. (NCI04) |
| Molecular Formula |
C7H9N5S
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|---|---|
| Molecular Weight |
195.2449
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| Exact Mass |
195.057
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| Elemental Analysis |
C, 43.06; H, 4.65; N, 35.87; S, 16.42
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| CAS # |
143621-35-6
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| Related CAS # |
143621-35-6 or236392-56-6
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| PubChem CID |
9571836
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| Appearance |
Light yellow to khaki solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
436.0±55.0 °C at 760 mmHg
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| Melting Point |
234°C(lit.)
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| Flash Point |
217.5±31.5 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.720
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| LogP |
0.98
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
13
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| Complexity |
205
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S=C(N([H])[H])N([H])/N=C(\[H])/C1=C(C([H])=C([H])C([H])=N1)N([H])[H]
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| InChi Key |
XMYKNCNAZKMVQN-NYYWCZLTSA-N
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| 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+
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| Chemical Name |
[(E)-(3-aminopyridin-2-yl)methylideneamino]thiourea
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| Synonyms |
3-AP; 33Apct; AIDS179996; NSC-663249; AIDS179996; AP; OCX191; PAN-811; OCX191; 3AP; NSC 663249; PAN811; NSC663249; Triapine; 3-AP; 236392-56-6; 143621-35-6; 200933-27-3; OCX 191; 2-((3-Aminopyridin-2-yl)methylene)hydrazinecarbothioamide; PAN-811; OCX 191; PAN 811
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~20 mg/mL (~102.4 mM)
Water : <1 mg/mL Ethanol : <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (12.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (12.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 4%DMSO+dd H2O: 10mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.1219 mL | 25.6095 mL | 51.2190 mL | |
| 5 mM | 1.0244 mL | 5.1219 mL | 10.2438 mL | |
| 10 mM | 0.5122 mL | 2.5610 mL | 5.1219 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02595879 | Active Recruiting |
Drug: Cisplatin Drug: Triapine |
Stage II Cervical Cancer AJCC v7 Advanced Vaginal Adenocarcinoma |
Universitätsklinikum Hamburg- Eppendorf |
October 2010 | Phase 2 Phase 3 |
| NCT04234568 | Active Recruiting |
Drug: Lutetium Lu 177 Dotatate Drug: Triapine |
Metastatic Neuroendocrine Tumor | National Cancer Institute (NCI) |
July 20, 2020 | Phase 1 |
| NCT02466971 | Active Recruiting |
Drug: Cisplatin Drug: Triapine |
Vaginal Carcinoma Vaginal Adenocarcinoma |
National Cancer Institute (NCI) |
May 10, 2016 | Phase 3 |
| NCT04494113 | Active Recruiting |
Procedure: Biopsy Drug: Triapine |
Endometrial Serous Adenocarcinoma | National Cancer Institute (NCI) |
February 8, 2022 | Phase 2 |
| NCT05724108 | Active Recruiting |
Drug: Lutetium Lu 177 Dotatate Drug: Triapine |
Metastatic Neuroendocrine Tumor | National Cancer Institute (NCI) |
August 30, 2023 | Phase 2 |
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