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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 of TEPOTINIB

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

Description
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.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
244.4 ng/mL
215 mg single, oral
dose: 215 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
301.3 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
442.4 ng/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
807.5 ng/mL
215 mg 1 times / day steady-state, oral
dose: 215 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
610.1 ng/mL
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
996.8 ng/mL
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1291 ng/mL
450 mg 1 times / day steady-state, oral
dose: 450 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
57 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
330 ng/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
863 ng/mL
1400 mg single, oral
dose: 1400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
113 ng/mL
30 mg 1 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
943 ng/mL
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
1805 ng/mL
1400 mg 1 times / day steady-state, oral
dose: 1400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
89 ng/mL
60 mg 3 times / week multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
178 ng/mL
130 mg 3 times / week multiple, oral
dose: 130 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
722 ng/mL
315 mg 3 times / week multiple, oral
dose: 315 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4060.8 ng × h/mL
215 mg single, oral
dose: 215 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5412.7 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8235 ng × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
16088.6 ng × h/mL
215 mg 1 times / day steady-state, oral
dose: 215 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13313.4 ng × h/mL
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
21509 ng × h/mL
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
27438 ng × h/mL
450 mg 1 times / day steady-state, oral
dose: 450 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
849 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
5918 ng × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
15542 ng × h/mL
1400 mg single, oral
dose: 1400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
2267 ng × h/mL
30 mg 1 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
20169 ng × h/mL
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
39284 ng × h/mL
1400 mg 1 times / day steady-state, oral
dose: 1400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
3032 ng × h/mL
60 mg 3 times / week multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
5306 ng × h/mL
130 mg 3 times / week multiple, oral
dose: 130 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
27760 ng × h/mL
315 mg 3 times / week multiple, oral
dose: 315 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEPOTINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
32 h
450 mg 1 times / day steady-state, oral
dose: 450 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
450 mg 1 times / day steady-state, oral
dose: 450 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TEPOTINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse 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...
AEs leading to
discontinuation/dose reduction:
Edema (5%)
Pleural effusion (2%)
Dyspnea (1.6%)
General health deterioration (1.6%)
Pneumonitis (1.2%)
Edema (23%)
Increased blood creatinine (6%)
Pleural effusion (4.3%)
Increased ALT (3.1%)
Pneumonia (2.4%)
Edema (19%)
Pleural effusion (2.7%)
Increased blood creatinine (2.7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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
Pleural effusion 2%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Pneumonia 2.4%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Increased blood creatinine 2.7%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Pleural effusion 2.7%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Edema 23%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Increased ALT 3.1%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Pleural effusion 4.3%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Edema 5%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
Increased blood creatinine 6%
Disc. AE
450 mg 1 times / day multiple, oral
Recommended
unhealthy, ADULT
PubMed

PubMed

TitleDatePubMed
EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors.
2013 Jun 1
Patents

Sample Use Guides

500 mg of tepotinib tablet once daily orally during each 21 day cycle
Route of Administration: Oral
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
Created
by admin
on Mon Mar 31 22:50:08 GMT 2025
Edited
by admin
on Mon Mar 31 22:50:08 GMT 2025
Record UNII
1IJV77EI07
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
tepotinib [INN]
Preferred Name English
TEPOTINIB
INN   WHO-DD  
INN   USAN  
Official Name English
MSC-2156119
Code 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
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
FDA ORPHAN DRUG 679719
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
Code System Code Type Description
DAILYMED
1IJV77EI07
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
PUBCHEM
25171648
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
EPA CompTox
DTXSID70149132
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
WIKIPEDIA
Tepotinib
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
DRUG BANK
DB15133
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
RXCUI
2477103
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
CAS
1100598-32-0
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
INN
9934
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
ChEMBL
CHEMBL3402762
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
FDA UNII
1IJV77EI07
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
USAN
HI-32
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
SMS_ID
100000175303
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
NCI_THESAURUS
C88314
Created by admin on Mon Mar 31 22:50:08 GMT 2025 , Edited by admin on Mon Mar 31 22:50:08 GMT 2025
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
CUMULATIVE EXCRETION
URINE
TARGET -> INHIBITOR
IC50
CUMULATIVE EXCRETION
FECAL
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
BINDER->LIGAND
Protein binding of tepotinib is 98% and is independent of drug concentration at clinically relevant exposures.
TARGET -> INHIBITOR
Tepotinib also inhibited melatonin 2 and imidazoline 1 receptors at clinically achievable concentrations.
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
URINE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TRANSPORTER -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION
PHARMACOKINETIC
IN PATIENTS WITH CANCER
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC