[CAS NO. 905854-02-6] Tivantinib

Ships within

Stock

Price

Qty

Total

$0.00

Please click "REQUEST A QUOTE" button if you need other sizes or custom synthesis

request a quote

If there is no stock, or you need other sizes or custom synthesis, please:

PRODUCTS SPECIFICATIONS [905854-02-6]

Catalog

HY-50686

Brand

MCE

CAS

905854-02-6

DESCRIPTION [905854-02-6]

Overview

MDL	MFCD11977597
Molecular Weight	369.42
Molecular Formula	C23H19N3O2
SMILES	O=C(NC1=O)[C@@H](C2=CN3C4=C(C=CC=C42)CCC3)[C@@H]1C5=CNC6=C5C=CC=C6

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

9 Publications Citing Use of MCE

Summary

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]

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 IC ₅₀ 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] .

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] .

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

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT00802555	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Cirrhosis\|Hepatocellular Carcinoma	January 2009	Phase 1
NCT01725191	National Cancer Institute (NCI)	Childhood Solid Neoplasm	October 2012	Phase 1
NCT02608411	Istituto Oncologico Veneto IRCCS	Carcinoma, Small Cell	October 2015	Phase 2
NCT01519414	National Cancer Institute (NCI)	Hormone-Resistant Prostate Cancer\|Prostate Adenocarcinoma\|Recurrent Prostate Carcinoma\|Stage IV Prostate Cancer	January 11, 2012	Phase 2
NCT00558207	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Pancreatic Neoplasms	November 2007	Phase 2
NCT02029157	Kyowa Kirin Co., Ltd.	Liver Cancer	January 2014	Phase 3
NCT01178411	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Advanced Solid Tumors	August 31, 2010	Phase 1\|Phase 2
NCT01861301	National Cancer Institute (NCI)	Epithelioid Mesothelioma\|Recurrent Malignant Mesothelioma\|Sarcomatoid Mesothelioma\|Stage II Pleural Mesothelioma\|Stage III Pleural Mesothelioma\|Stage IV Pleural Mesothelioma	January 2013	Phase 2
NCT00612209	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Cancer, Advanced Solid Tumors	April 2007	Phase 1
NCT01656265	Kyowa Kirin Co., Ltd.	Advanced Hepatocellular Carcinoma	July 2012	Phase 1
NCT01070290	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Gastric Cancer		Phase 2
NCT01152645	Kyowa Kirin Co., Ltd.	Gastric Cancer	June 2010	Phase 2
NCT00609921	Kyowa Kirin Co., Ltd.	Cancer	January 2008	Phase 1
NCT02150733	Daiichi Sankyo, Inc.\|Medpace, Inc.	Hepatic Impairment\|Solid Tumor\|Cancer	April 2014	Phase 1
NCT01699061	Daiichi Sankyo, Inc.\|Medpace, Inc.	Solid Tumors	July 2012	Phase 1
NCT02049060	Armando Santoro, MD\|Istituto Clinico Humanitas	Malignant Pleural Mesothelioma\|Nonsquamous Nonsmall Cell Neoplasm of Lung	January 2013	Phase 1\|Phase 2
NCT01075048	Daiichi Sankyo, Inc.	Metastatic Colorectal Cancer	January 26, 2010	Phase 1\|Phase 2
NCT01395758	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Metastatic Non-Small Cell Lung Cancer	July 2011	Phase 2
NCT00651638	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Healthy	March 2008	Phase 1
NCT01517399	Daiichi Sankyo, Inc.\|Medpace, Inc.	Solid Tumors	December 2011	Phase 1
NCT01251796	Kyowa Kirin Co., Ltd.	Advanced+Recurrent Non-small-cell Lung Cancer	December 2010	Phase 1
NCT01468922	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	Solid Tumor	January 23, 2012	Phase 1
NCT00874042	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Advanced Solid Tumors	March 2009	Phase 1
NCT01688973	National Cancer Institute (NCI)	Recurrent Renal Cell Carcinoma\|Stage III Renal Cell Cancer\|Stage IV Renal Cell Cancer\|Type 1 Papillary Renal Cell Carcinoma\|Type 2 Papillary Renal Cell Carcinoma	August 20, 2012	Phase 2
NCT01055067	Daiichi Sankyo, Inc.	Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas)	February 2, 2010	Phase 2
NCT01580735	Kyowa Kirin Co., Ltd.	Non-small-cell Lung Cancer	May 2012	Phase 2
NCT00557609	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Renal Cell Carcinoma (RCC)\|Alveolar Soft Part Sarcoma (ASPS)\|Clear Cell Sarcoma (CCS)	October 2007	Phase 2
NCT01755767	Daiichi Sankyo, Inc.\|ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Hepatocellular Carcinoma	December 27, 2012	Phase 3
NCT00658554	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Healthy	April 2008	Phase 1
NCT00302172	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Cancer\|Tumor	January 2006	Phase 1
NCT01069757	Kyowa Kirin Co., Ltd.	Non-small-cell Lung Cancer	February 2010	Phase 1
NCT01377376	Kyowa Kirin Co., Ltd.	Non-small-cell Lung Cancer	July 2011	Phase 3
NCT01575522	National Cancer Institute (NCI)	Estrogen Receptor Negative\|HER2+Neu Negative\|Progesterone Receptor Negative\|Recurrent Breast Carcinoma\|Stage IV Breast Cancer\|Triple-Negative Breast Carcinoma	March 2012	Phase 2
NCT01696955	National Cancer Institute (NCI)	Head and Neck Squamous Cell Carcinoma\|Recurrent Head and Neck Carcinoma	August 20, 2012	Phase 2
NCT01244191	Daiichi Sankyo, Inc.\|ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Non Squamous, Non-small-cell Lung Cancer	January 11, 2011	Phase 3
NCT00988741	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Unresectable Hepatocellular Carcinoma	September 2009	Phase 2
NCT00827177	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Advanced Solid Tumors	September 2009	Phase 1
NCT01892527	Armando Santoro, MD\|Istituto Clinico Humanitas	Colorectal Cancer Metastatic\|C-met Overexpression	March 2013	Phase 2
NCT01149720	Daiichi Sankyo, Inc.\|ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)\|ICON Clinical Research	Solid Tumors	July 2010	Phase 1
NCT00612703	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Cancer	February 2008	Phase 1
NCT01654965	National Cancer Institute (NCI)	Adult Solid Neoplasm	July 24, 2012	Phase 1
NCT00777309	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)	Non Small Cell Lung Cancer	September 2008	Phase 2
NCT01611857	SCRI Development Innovations, LLC\|Daiichi Sankyo, Inc.	Malignant Solid Tumour\|Gastroesophageal Cancer	July 2012	Phase 1\|Phase 2
NCT01749384	National Cancer Institute (NCI)	Solid Neoplasm	December 6, 2012	Phase 1
NCT01447914	National Cancer Institute (NCI)	Refractory Multiple Myeloma	November 2011	Phase 2
NCT01625156	National Cancer Institute (NCI)	Adult Solid Neoplasm	May 2012	Phase 1

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL ( 270.69 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

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.

In Vivo:

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

* All of the co-solvents are available by MCE.

References

Synonyms

2,5-Pyrrolidinedione, 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-, (3R,4R)-

(3R,4R)-3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-2,5-pyrrolidinedione

(3R,4R)-3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione

Tivantinib

ARQ 197