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

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

Molecular Formula	C29H28N6O2
Molecular Weight	492.5716
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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 56	Inhibitor 8,504		3.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lung adenocarcinoma 8	Primary		Phase II 1,147	Unknown

C_max

Value	Dose	Analyte	Population
244.4 ng/mL	215 mg single, oral	TEPOTINIB plasma	Homo sapiens
301.3 ng/mL	300 mg single, oral	TEPOTINIB plasma	Homo sapiens
442.4 ng/mL	500 mg single, oral	TEPOTINIB plasma	Homo sapiens
807.5 ng/mL	215 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
610.1 ng/mL	300 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
996.8 ng/mL	500 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
1291 ng/mL	450 mg 1 times / day steady-state, oral	TEPOTINIB unknown	Homo sapiens
57 ng/mL	30 mg single, oral	TEPOTINIB plasma	Homo sapiens
330 ng/mL	500 mg single, oral	TEPOTINIB plasma	Homo sapiens
863 ng/mL	1400 mg single, oral	TEPOTINIB plasma	Homo sapiens
113 ng/mL	30 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
943 ng/mL	500 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
1805 ng/mL	1400 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
89 ng/mL	60 mg 3 times / week multiple, oral	TEPOTINIB plasma	Homo sapiens
178 ng/mL	130 mg 3 times / week multiple, oral	TEPOTINIB plasma	Homo sapiens
722 ng/mL	315 mg 3 times / week multiple, oral	TEPOTINIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
4060.8 ng × h/mL	215 mg single, oral	TEPOTINIB plasma	Homo sapiens
5412.7 ng × h/mL	300 mg single, oral	TEPOTINIB plasma	Homo sapiens
8235 ng × h/mL	500 mg single, oral	TEPOTINIB plasma	Homo sapiens
16088.6 ng × h/mL	215 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
13313.4 ng × h/mL	300 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
21509 ng × h/mL	500 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
27438 ng × h/mL	450 mg 1 times / day steady-state, oral	TEPOTINIB unknown	Homo sapiens
849 ng × h/mL	30 mg single, oral	TEPOTINIB plasma	Homo sapiens
5918 ng × h/mL	500 mg single, oral	TEPOTINIB plasma	Homo sapiens
15542 ng × h/mL	1400 mg single, oral	TEPOTINIB plasma	Homo sapiens
2267 ng × h/mL	30 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
20169 ng × h/mL	500 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
39284 ng × h/mL	1400 mg 1 times / day steady-state, oral	TEPOTINIB plasma	Homo sapiens
3032 ng × h/mL	60 mg 3 times / week multiple, oral	TEPOTINIB plasma	Homo sapiens
5306 ng × h/mL	130 mg 3 times / week multiple, oral	TEPOTINIB plasma	Homo sapiens
27760 ng × h/mL	315 mg 3 times / week multiple, oral	TEPOTINIB plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
32 h	450 mg 1 times / day steady-state, oral		TEPOTINIB unknown	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%	450 mg 1 times / day steady-state, oral		TEPOTINIB unknown	Homo sapiens

Doses

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Dose	Population	Adverse events
1400 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT	DLT: fatigue...
450 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT	Disc. AE: Edema, Pleural effusion...

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AEs

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AE	Significance	Dose	Population
fatigue	grade 3, 14.3% DLT	1400 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Pneumonitis	1.2% Disc. AE	450 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
Dyspnea	1.6% Disc. AE	450 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
General health deterioration	1.6% Disc. AE	450 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT
Edema	19% Disc. AE	450 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT

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PubMed

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

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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.

Substance Class	Chemical
Record UNII	1IJV77EI07
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

tepotinib [INN]

Preferred Name

English

TEPOTINIB

Official Name

English

MSC-2156119

Code

English

MSC2156119

Code

English

EMD-1214063

Code

English

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Classification Tree

Code System

Code

Protein Kinase Inhibitor

NCI_THESAURUS

C1967

Designated/Approved

FDA ORPHAN DRUG

679719

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

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Code System

Code

Type

Description

DAILYMED

1IJV77EI07

PRIMARY

PUBCHEM

25171648

PRIMARY

EPA CompTox

DTXSID70149132

PRIMARY

WIKIPEDIA

Tepotinib

PRIMARY

DRUG BANK

DB15133

PRIMARY

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Related Record

Type

Details


					8B73AZL5XP

TEPOTINIB HYDROCHLORIDE ANHYDROUS

SALT/SOLVATE -> PARENT

Amount:


					1IJV77EI07

TEPOTINIB

CUMULATIVE EXCRETION

Qualification:

URINE

Amount:

MOLE PERCENT OF AMOUNT ADMINISTERED 14.4 [9 to 18] (average)
MEDIAN VALUE


					QA085PMU8Q

HEPATOCYTE GROWTH FACTOR RECEPTOR

TARGET -> INHIBITOR

Qualification:

IC50

Amount:

4 NANOMOLAR (average)


					1IJV77EI07

TEPOTINIB

CUMULATIVE EXCRETION

Qualification:

FECAL

Amount:

MOLE PERCENT OF AMOUNT ADMINISTERED 78.7 % [69 to 83] (average)
MEDIAN VALUE


					22ES734693

MULTIDRUG RESISTANCE PROTEIN 1

TRANSPORTER -> INHIBITOR

Amount:

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Related Record

Type

Details


					1IJV77EI07

TEPOTINIB

ACTIVE MOIETY

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Name	Property Type	Amount	Referenced Substance	Parameters
Tmax	PHARMACOKINETIC	8 hours [6 to 12] (average)	`1IJV77EI07` TEPOTINIB

Biological Half-life	PHARMACOKINETIC	32 hours (average)	`1IJV77EI07` TEPOTINIB	ORAL ADMINISTRATION PHARMACOKINETIC IN PATIENTS WITH CANCER PHARMACOKINETIC

Volume of Distribution	PHARMACOKINETIC	1038 LITERS (average)	`1IJV77EI07` TEPOTINIB

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound