Tivantinib
Based on 10 publication(s) in Google Scholar
Tivantinib is a highly selective c-Met tyrosine kinase inhibitor with a Ki of 355 nM.
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- Pureté: 99.61%
- CAS No.: 905854-02-6
- Formule: C23H19N3O2
- Masse moléculaire:369.42
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Tivantinib
More- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- J Pharm Anal. 2021 Dec;11(6):799-807. [Abstract]
- Pharmaceuticals (Basel). 2024 Oct 9;17(10):1350. [Abstract]
- Cancers (Basel). 2022 Mar 19;14(6):1575. [Abstract]
- Oncol Rep. 2018 Aug;40(2):635-646. [Abstract]
- Cancer Res Treat. 2020 Jul;52(3):973-986. [Abstract]
- FEBS J. 2016 Jan;283(1):102-11. [Abstract]
- J Cancer Res Clin Oncol. 2021 Jan;147(1):167-175. [Abstract]
- Patent. US20240263208A1.
- Patent. US20210299273A1.
Activité biologique
Description
IC50 & Target
Ki: 355 nM (c-Met)[1]
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
0.59 μM
Compound: 99; ARQ 197
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Antiproliferative activity against human A549 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
Antiproliferative activity against human A549 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
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[PMID: 37262349] |
| MKN-45 | IC50 |
0.58 μM
Compound: 99; ARQ 197
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Antiproliferative activity against human MKN-45 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
Antiproliferative activity against human MKN-45 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
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[PMID: 37262349] |
| NCI-H441 | IC50 |
0.3 μM
Compound: 99; ARQ 197
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Antiproliferative activity against human NCI-H441 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
Antiproliferative activity against human NCI-H441 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
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[PMID: 37262349] |
| NCI-H460 | IC50 |
0.6 μM
Compound: 99; ARQ 197
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Antiproliferative activity against human NCI-H460 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
Antiproliferative activity against human NCI-H460 cells assessed as inhibition of cell growth measured after 48 hrs by MTS assay
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[PMID: 37262349] |
In Vitro
Tivantinib (ARQ 197) selectively inhibits c-Met activity in cell-free and cell-based assays. c-Met-expressing cancer cell lines treated with Tivantinib display either a dose-dependent loss of proliferative capacity or caspase-dependent apoptosis that positively correlates with either ligand-dependent c-Met activity or constitutively active c-Met. To examine the biochemical mode of inhibition of Tivantinib, kinetic analyses are done using recombinant human c-Met in a filtermat-based assay. The Km of ATP is 50.5±2.2 μM, which is similar to the Km value of ATP. In these kinetic studies, Tivantinib inhibits human recombinant c-Met with a calculated inhibitory constant (Ki) of ~355 nM. In vitro exposure to Tivantinib inhibits constitutive c-Met phosphorylation in HT29 and MKN-45 cells, and HGF-induced c-Met phosphorylation in MDA-MB-231 and NCI-H441 cells with an IC50 of 100 to 300 nM[1]. Tivantinib is a low-molecular-weight compound, and is the first in class orally available selective inhibitor of c-Met[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 905854-02-6
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Appearance Solid
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Masse moléculaire 369.42
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Formule C23H19N3O2
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Color Light brown to brown
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SMILES
O=C(NC1=O)[C@@H](C2=CN3C4=C(C=CC=C42)CCC3)[C@@H]1C5=CNC6=C5C=CC=C6
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Synonyms
ARQ 197; (3R,4R)-ARQ 198
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (10)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
J Pharm Anal
Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells. [Abstract]2021 Dec;11(6):799-807. PMID: 35028186 -
Pharmaceuticals (Basel)
Repurposing of c-MET Inhibitor Tivantinib Inhibits Pediatric Neuroblastoma Cellular Growth. [Abstract]2024 Oct 9;17(10):1350. PMID: 39458991 -
Cancers (Basel)
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening. [Abstract]2022 Mar 19;14(6):1575. PMID: 35326726 -
Oncol Rep
Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues. [Abstract]2018 Aug;40(2):635-646. PMID: 29917168 -
Cancer Res Treat
RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer. [Abstract]2020 Jul;52(3):973-986. PMID: 32324988 -
FEBS J
Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery. [Abstract]2016 Jan;283(1):102-11. PMID: 26462166 -
J Cancer Res Clin Oncol
MET canonical transcript expression is a predictive biomarker for chemo-sensitivity to MET-inhibitors in hepatocellular carcinoma cell lines. [Abstract]2021 Jan;147(1):167-175. PMID: 32980960 -
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Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (270.69 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
Kinase Assay[1]
Recombinant c-Met protein (50 ng) comprising residues 974 to 1390 is incubated in a reaction buffer [50 mM Tris-HCl (pH 7.5), 2 mM DTT, 0.1 mM Na3VO4, 10 mM MgCl2, 1 mM EGTA, 0.02 mg/mL bovine serum albumin, and 10% glycerol] with various concentrations of Tivantinib or DMSO in a total volume of 20 μL. After incubating for 20 minutes at room temperature, 20 μL of 20 μM poly-Glu-Tyr substrate and 20 μL of increasing amounts of cold ATP containing 1.5 μCi of [γ-33P]ATP are added to initiate the reaction. The reaction is stopped after 5, 10, 20, 40, and 60 minutes by the addition of 10% phosphoric acid and 10 μL aliquots of the reaction mixture are spotted onto P30 filtermat in triplicate. The filters are washed thrice for 5 minutes with 0.75% phosphoric acid and once with methanol for 2 minutes. The level of radioactivity is determined by using a Wallac TriLux MicroBeta liquid scintillation counter. Nonspecific binding is determined by conducting the assay in the absence of enzyme and then subtracting the value from each of the experimental values. Reaction rates are determined in the linear range of each reaction and GraphPad Prism software is used to calculate the Km and Vmax values[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay[1]
HT29, MKN-45, MDA-MB-231, and NCI-H441 (lung cancer) human cancer cells are seeded in 96-well plates overnight in a medium with 10% FBS. Each cell line is optimized for seeding cell number to ensure a similar degree of confluence at the end of the experiment in nontreated (control) wells. The next day, cells are treated with different concentrations of Tivantinib for 24 hours at 37°C. After ARQ 197 treatment, the drug-containing medium is removed, and cells are washed twice with PBS and incubated in a drug-free medium for an additional 48 hours. Cells are then incubated and stained for 4 hours with the MTS reagent (final concentration of 0.5 mg/mL) per well and are lysed. The results are quantitated by spectrophotometry at λ=450 nm[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
Female athymic nude mice are acclimated to the animal housing facility for at least 1 week before the study. Efficacy studies are done in athymic mice bearing HT29, MKN-45, or MDA-MB-231 tumor xenografts to determine the effect of ARQ 197 on tumor growth. Tumor cells [5×106 (HT29) and 8×106 (MKN-45 and MDA-MB-231) cells/animal] are inoculated s.c. on day 0. Tumor dimensions are measured by a digital caliper and tumor volumes are calculated as length×width2/2. When tumors reached a volume of ~100 mm3, mice are randomized into groups and treated daily with orally administered vehicle control or 200 mg/kg Tivantinib formulated in polyethylene glycol 400/20% Vitamin E tocopheryl polyethylene glycol succinate (60:40) at 30 mg/mL, for 5 consecutive days, followed by a 2-day dosing holiday for four cycles. Therefore, each animal received a total of 20 doses. Results are expressed as mean tumor volume±SEM. To assess differences in tumor size between groups, a Mann-Whitney nonparametric t test is performed and significance is defined as P<0.05.
Rats[2]
Six male Sprague-Dawley rats (180-220 g) are used to study the pharmacokinetics of Tivantinib. Diet is prohibited for 12 h before the experiment but water is freely available. Blood samples (0.3 mL) are collected from the tail vein into heparinized 1.5 mL polythene tubes at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h after oral administration of Tivantinib (10 mg/kg). The samples are immediately centrifuged at 4000g for 8 min. The plasma obtained (100 μL) is stored at -20°C until analysis. Plasma Tivantinib concentration versus time data for each rat is analyzed by DAS (Drug and statistics) software.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureté et documentation
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Fiche technique (289 KB)
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SDS (644 KB)
- English - EN (644 KB)
- Français - FR (644 KB)
- Deutsch - DE (644 KB)
- Norwegian - NO (644 KB)
- Español - ES (644 KB)
- Swedish - SV (644 KB)
- Italian - IT (644 KB)
- Korean - KR (644 KB)
- Portuguese - PT (644 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Munshi N, et al. ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity. Mol Cancer Ther. 2010 Jun;9(6):1544-53. [Content Brief]
[2]. Bai YL, et al. Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry. J Pharm Biomed Anal. 2016 Jul 15;126:98-102. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7069 mL | 13.5347 mL | 27.0695 mL | 67.6736 mL |
| 5 mM | 0.5414 mL | 2.7069 mL | 5.4139 mL | 13.5347 mL | |
| 10 mM | 0.2707 mL | 1.3535 mL | 2.7069 mL | 6.7674 mL | |
| 15 mM | 0.1805 mL | 0.9023 mL | 1.8046 mL | 4.5116 mL | |
| 20 mM | 0.1353 mL | 0.6767 mL | 1.3535 mL | 3.3837 mL | |
| 25 mM | 0.1083 mL | 0.5414 mL | 1.0828 mL | 2.7069 mL | |
| 30 mM | 0.0902 mL | 0.4512 mL | 0.9023 mL | 2.2558 mL | |
| 40 mM | 0.0677 mL | 0.3384 mL | 0.6767 mL | 1.6918 mL | |
| 50 mM | 0.0541 mL | 0.2707 mL | 0.5414 mL | 1.3535 mL | |
| 60 mM | 0.0451 mL | 0.2256 mL | 0.4512 mL | 1.1279 mL | |
| 80 mM | 0.0338 mL | 0.1692 mL | 0.3384 mL | 0.8459 mL | |
| 100 mM | 0.0271 mL | 0.1353 mL | 0.2707 mL | 0.6767 mL |
Tivantinib Related Classifications
HY-50686 Related Classifications
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