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Details

Stereochemistry ACHIRAL
Molecular Formula C33H37F2N7O4
Molecular Weight 633.6882
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GOLVATINIB

SMILES

CN1CCN(CC1)C2CCN(CC2)C(=O)NC3=NC=CC(OC4=CC=C(NC(=O)C5(CC5)C(=O)NC6=CC=C(F)C=C6)C(F)=C4)=C3

InChI

InChIKey=UQRCJCNVNUFYDX-UHFFFAOYSA-N
InChI=1S/C33H37F2N7O4/c1-40-16-18-41(19-17-40)24-9-14-42(15-10-24)32(45)39-29-21-26(8-13-36-29)46-25-6-7-28(27(35)20-25)38-31(44)33(11-12-33)30(43)37-23-4-2-22(34)3-5-23/h2-8,13,20-21,24H,9-12,14-19H2,1H3,(H,37,43)(H,38,44)(H,36,39,45)

HIDE SMILES / InChI
Molecular Formula C33H37F2N7O4
Molecular Weight 633.6882
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.cancer.gov/publications/dictionaries/cancer-drug?cdrid=640626 https://www.ncbi.nlm.nih.gov/pubmed/19832844

Golvatinib is a highly potent, small-molecule, ATP-competitive inhibitor of c-Met and multiple members of the Eph receptor family plus c-Kit and Ron. Eisai was developing an oral formulation of golvatinib, which acts as both a c-Met inhibitor and a vascular endothelial growth factor receptor 2 antagonist with potential antineoplastic activity. Golvatinib binds to and inhibits the activities of both c-Met and VEGFR-2, which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of various tumor cell types and play important roles in tumor cell growth, migration and angiogenesis. Clinical trials involving several forms of cancer are currently underway.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 20.0 nM [IC50]
Antagonist
2849
 40.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
9730 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/25278451
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GOLVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
171000 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25278451
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GOLVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
171000 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/25278451
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GOLVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
45 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25278451
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GOLVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
45 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/25278451
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GOLVATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
450 mg 1 times / day multiple, oral
Highest studied dose
Dose: 450 mg, 1 times / day
Route: oral
Route: multiple
Dose: 450 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
DLT: Fatigue, Fatigue...
Disc. AE: Vomiting...
Dose limiting toxicities:
Fatigue (grade 2, 50%)
Fatigue (grade 3, 50%)
AEs leading to
discontinuation/dose reduction:
Vomiting (50%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
200 mg 2 times / day multiple, oral
MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
400 mg 1 times / day multiple, oral
MTD
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
Disc. AE: Fatigue, Anorexia...
AEs leading to
discontinuation/dose reduction:
Fatigue (12.5%)
Anorexia (12.5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
300 mg 2 times / day multiple, oral
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
DLT: ALT increased...
Other AEs: Vomiting, Nausea...
Dose limiting toxicities:
ALT increased (grade 3, 50%)
Other AEs:
Vomiting (grade 2, 50%)
Nausea (grade 2, 50%)
Anorexia (grade 2, 50%)
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
AEs

AEs

AESignificanceDosePopulation
Vomiting 50%
Disc. AE
450 mg 1 times / day multiple, oral
Highest studied dose
Dose: 450 mg, 1 times / day
Route: oral
Route: multiple
Dose: 450 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
Fatigue grade 2, 50%
DLT, Disc. AE
450 mg 1 times / day multiple, oral
Highest studied dose
Dose: 450 mg, 1 times / day
Route: oral
Route: multiple
Dose: 450 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
Fatigue grade 3, 50%
DLT, Disc. AE
450 mg 1 times / day multiple, oral
Highest studied dose
Dose: 450 mg, 1 times / day
Route: oral
Route: multiple
Dose: 450 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
Anorexia 12.5%
Disc. AE
400 mg 1 times / day multiple, oral
MTD
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
Fatigue 12.5%
Disc. AE
400 mg 1 times / day multiple, oral
MTD
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/25278451
Anorexia grade 2, 50%
300 mg 2 times / day multiple, oral
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
Nausea grade 2, 50%
300 mg 2 times / day multiple, oral
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
Vomiting grade 2, 50%
300 mg 2 times / day multiple, oral
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
ALT increased grade 3, 50%
DLT
300 mg 2 times / day multiple, oral
Studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3079
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252
inhibitor
2438
inhibitor
2507

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1741
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C9
2497
 inconclusive [IC50 21.3174 uM]
P-gp
1932
 inconclusive [IC50 25.929 uM]
CYP2D6
2546
 inconclusive [IC50 6.7412 uM]
CYP3A4
2633
 yes [IC50 26.837 uM]
PubMed

PubMed

TitleDatePubMed
E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models.
2010 Jan
Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells.
2012 Jul 1
Patents

Patents

07790885
4
07855290
3
08288538
2
20080319188
2
20100075944
2

Sample Use Guides

In Vivo Use Guide
Golvatinib at the MTD of 400 mg once daily was well tolerated with pharmacodynamic evidence of c-Met target modulation.
Route of Administration: Oral
In Vitro Use Guide
Golvatinib strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively
Substance Class Chemical
Created
by admin
on Mon Mar 31 20:58:43 GMT 2025
Edited
by admin
on Mon Mar 31 20:58:43 GMT 2025
Record UNII
516Z3YP58E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
E-7050
Preferred Name English
GOLVATINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
GOLVATINIB [USAN]
Common Name English
1,1-CYCLOPROPANEDICARBOXAMIDE, N-(2-FLUORO-4-((2-(((4-(4-METHYL-1-PIPERAZINYL)-1-PIPERIDINYL)CARBONYL)AMINO)-4-PYRIDINYL)OXY)PHENYL)-N'-(4-FLUOROPHENYL)-
Systematic Name English
Golvatinib [WHO-DD]
Common Name English
E7050
Code English
golvatinib [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
NCI_THESAURUS C1404
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
Code System Code Type Description
SMS_ID
100000163704
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
NCI_THESAURUS
C82363
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
FDA UNII
516Z3YP58E
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
CAS
928037-13-2
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
PUBCHEM
16118392
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
DRUG BANK
DB11977
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
INN
9565
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
EVMPD
SUB178048
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
USAN
YY-85
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
EPA CompTox
DTXSID40239155
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
ChEMBL
CHEMBL3039525
Created by admin on Mon Mar 31 20:58:43 GMT 2025 , Edited by admin on Mon Mar 31 20:58:43 GMT 2025
PRIMARY
Related Record Type Details
Structure of GOLVATINIB TARTRATE
SALT/SOLVATE -> PARENT
Structure of PP-121
TARGET -> INHIBITOR
Related Record Type Details
Structure of GOLVATINIB
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