Free shipping on all orders over $ 500

ARQ-197

Cat. No. M1811
ARQ-197 Structure
Synonym:

Tivantinib, ARQ197

Size Price Availability Quantity
10mg USD 95 In stock
50mg USD 300 In stock
200mg USD 720 In stock
Bulk Inquiry?

Quality Control
Biological Activity

ARQ-197 (Tivantinib) is a selective and oral small-molecule inhibitor of c-Met with a minimal IC50 value of 0.1 μM. c-Met, a key cell surface receptor tyrosine kinase involved in diverse regulatory functions, is often aberrantly activated in human cancers. While the precise mechanism of action of ARQ-197 remains undefined, data from preclinical studies have demonstrated that ARQ-197 inhibits c-Met activation in numerous human tumor cell lines and specifically targets c-Met in various cancer types; uniquely, ARQ-197 inhibits c-Met in a non-ATP-competitive manner. Phase I/II clinical trials demonstrated promise in terms of both tolerability and tumor response. Intriguingly, dose-limiting adverse effects were hematological in nature. Combinational trials are also ongoing to take advantage of the signaling crosstalk between c-Met and other oncogenic signaling systems. Prioritization of the clinical development of c-Met inhibitors, such as ARQ-197, among different tumor disease types is a key challenge at present; an improved understanding of the prediction of molecular determinants in tumors with respect to c-Met kinase as the driver oncogenic receptor, and of the prediction of tumor response, is still urgently needed.

Protocol
Cell Experiment
Cell lines SK-MEL-28, NCI-H661, NCI-H446, DLD-1, A549, SK-OV-3, NCI-H460, A375, NCI-H441, HT29, MKN-45, and MDA-MB-231 cells
Preparation method Cell proliferation assay
Cells were seeded in 96-well plates overnight in a medium with 10% FBS. Each cell line was 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 were treated with different concentrations of ARQ 197 for 24 hours at 37°C. After ARQ 197 treatment, the drug-containing medium was removed, and cells were washed twice with PBS and incubated in a drug-free medium for an additional 48 hours. Cells were then incubated and stained for 4 hours with the MTS reagent (final concentration of 0.5 mg/mL; Promega) per well and were lysed. The results were quantitated by spectrophotometry at λ = 450 nm.
Concentrations 0.03–10 μmol/L
Incubation time 24 h
Animal Experiment
Animal models athymic mice bearing HT29, MKN-45, or MDA-MB-231 tumor xenografts
Formulation polyethylene glycol 400/20% Vitamin E tocopheryl polyethylene glycol succinate (60:40) at 30 mg/mL
Dosages 200 mg/kg for 5 consecutive days weekly for four cycles
Administration orally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 369.42
Formula C23H19N3O2
CAS Number 905854-02-6
Purity >100.00%
Solubility DMSO
Storage at -20°C
References

ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity.
Munshi N, et al. Mol Cancer Ther. 2010 Jun;9(6):1544-53. PMID: 20484018.

Related c-Met Products
AMG 337

AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor.

S49076

S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nmol/L.

DCC2701

Altiratinib(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro.

MK-2461

MK-2461 is a potent, multi-targeted inhibitor for c-Met(WT/mutants) with IC50 of 0.4-2.5 nM, less potent to Ron, Flt1; 8- to 30-fold greater selectivity of c-Met targets versus FGFR1, FGFR2, FGFR3, PDGFRβ, KDR, Flt3, Flt4, TrkA, and TrkB.

NVP-BVU972

NVP-BVU972 is a selective and potent Met inhibitor with IC50 of 14 nM.

  Catalog
Abmole Inhibitor Catalog 2017




Keywords: ARQ-197, Tivantinib, ARQ197 supplier, c-Met, inhibitors

Contact Us

Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.