Cat. No.: HY-50686

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Tivantinib

(Synonyms: ARQ 197; (3R,4R)-ARQ 198)

10 Cited Publications

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Based on 10 publication(s) in Google Scholar

Tivantinib is a highly selective c-Met tyrosine kinase inhibitor with a K_i of 355 nM.

For research use only. We do not sell to patients.

Purity: 99.61%
CAS No.: 905854-02-6
Formula: C₂₃H₁₉N₃O₂
Molecular Weight:369.42

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Tivantinib Chemical Structure

CAS No.: 905854-02-6

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (10)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

Tivantinib is a highly selective c-Met tyrosine kinase inhibitor with a K_i of 355 nM.

IC₅₀ & Target

Ki: 355 nM (c-Met)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	0.59 μM Compound: 99; ARQ 197	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	[PMID: 37262349]
MKN-45	IC₅₀	0.58 μM Compound: 99; ARQ 197	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	[PMID: 37262349]
NCI-H441	IC₅₀	0.3 μM Compound: 99; ARQ 197	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	[PMID: 37262349]
NCI-H460	IC₅₀	0.6 μM Compound: 99; ARQ 197	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	[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 K_m of ATP is 50.5±2.2 μM, which is similar to the K_m value of ATP. In these kinetic studies, Tivantinib inhibits human recombinant c-Met with a calculated inhibitory constant (K_i) 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

Pharmacodynamically, the phosphorylation of c-Met in human colon xenograft tumors (HT29) is strongly inhibited by Tivantinib (ARQ 197), as assessed by a dramatic reduction of c-Met autophosphorylation 24 hours after a single oral dose of 200 mg/kg of Tivantinib. This same dosage in mice shows that tumor xenografts are exposed to sustained plasma levels of Tivantinib, consistent with the observed pharmacodynamic inhibition of c-Met phosphorylation and inhibition of proliferation of c-Met harboring cancer cell lines. A C_max of 5.73 μg/mL (13 μM), an area under the concentration-time curve of 12.1 μg/mL h, and a t_1/2 of 2.4 hours are measured. Plasma levels of Tivantinib 10 hours after dosing are determined to be 1.3 μM, >3-fold above the biochemical inhibitory constant of Tivantinib for c-Met^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 905854-02-6
Appearance Solid
Molecular Weight 369.42
Formula C₂₃H₁₉N₃O₂
Color Light brown to brown
SMILES

O=C(NC1=O)[C@@H](C2=CN3C4=C(C=CC=C42)CCC3)[C@@H]1C5=CNC6=C5C=CC=C6
Synonyms

ARQ 197; (3R,4R)-ARQ 198
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

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
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
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
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
Patent

US20240263208A1.
Patent

US20210299273A1.

Solvent & Solubility

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.7069 mL

13.5347 mL

27.0695 mL

5 mM

0.5414 mL

2.7069 mL

5.4139 mL

10 mM

0.2707 mL

1.3535 mL

2.7069 mL

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.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Protocol

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 K_m and V_max 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.

Animal Administration^[1]^[2]

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.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (289 KB)
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)
- Portuguese - PT (644 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

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Tivantinib

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Publications Citing Use of MedChemExpress (MCE) Tivantinib

Biological Activity

Chemical Information

Publications (10)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Tivantinib Related Classifications

Cat. No.: HY-50686