TEPOTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H28N6O2
Molecular Weight	492.5716
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC(COC2=CN=C(N=C2)C3=CC(CN4N=C(C=CC4=O)C5=CC(=CC=C5)C#N)=CC=C3)CC1

InChI

InChIKey=AHYMHWXQRWRBKT-UHFFFAOYSA-N

InChI=1S/C29H28N6O2/c1-34-12-10-21(11-13-34)20-37-26-17-31-29(32-18-26)25-7-3-5-23(15-25)19-35-28(36)9-8-27(33-35)24-6-2-4-22(14-24)16-30/h2-9,14-15,17-18,21H,10-13,19-20H2,1H3

HIDE SMILES / InChI

Description
Sources: http://biopharma.merckgroup.com/en/research_development/pipeline/pipeline.html
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25736998 https://www.ncbi.nlm.nih.gov/pubmed/23553846

Tepotinib is an investigational small molecule inhibitor of the c-Met receptor tyrosine kinase. Alterations of the c-Met signaling pathway are found in various cancer types and correlate with aggressive tumor behavior and poor clinical prognosis. Tepotinib is a potent and selective c-Met inhibitor, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib is currently in Phase I/II trials in liver cancer and lung cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25736998 \| https://www.ncbi.nlm.nih.gov/pubmed/23553846	Inhibitor 8297		3.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lung adenocarcinoma 8 Sources: https://clinicaltrials.gov/ct2/show/NCT02864992	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors.	2013 Jun 1	23553846

Patents

Sample Use Guides

In Vivo Use Guide

500 mg of tepotinib tablet once daily orally during each 21 day cycle

Route of Administration: Oral

In Vitro Use Guide

Tepotinib inhibits HGF-induced c-Met phosphorylation in A549 cells with IC50 of 6 nM. Treatment with Tepotinib induces a marked reduction of c-Met–constitutive phosphorylation in EBC-1 cells with IC50 of 9 nM. Tepotinib effectively blocks phosphorylation of the major downstream effectors of the c-Met enzyme, such as Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase, in EBC-1, MKN-45, and Hs746T cells in the range of 1 to 10 nM.

Name

Type

Language

TEPOTINIB

Official Name

English

MSC-2156119

Code

English

tepotinib [INN]

Common Name

English

MSC2156119

Code

English

EMD-1214063

Code

English

Tepotinib [WHO-DD]

Common Name

English

EMD1214063

Code

English

TEPOTINIB [USAN]

Common Name

English

MSC-2156119J

Code

English

BENZONITRILE, 3-(1,6-DIHYDRO-1-((3-(5-((1-METHYL-4-PIPERIDINYL)METHOXY)-2-PYRIMIDINYL)PHENYL)METHYL)-6-OXO-3-PYRIDAZINYL)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1967