U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C29H29F3N8O.CH4O3S
Molecular Weight 658.694
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUMATINIB MESYLATE

SMILES

CS(O)(=O)=O.CN1CCN(CC2=C(C=C(C=C2)C(=O)NC3=CC(NC4=NC(=CC=N4)C5=CN=CC=C5)=C(C)N=C3)C(F)(F)F)CC1

InChI

InChIKey=ZSASDYCFROUKTJ-UHFFFAOYSA-N
InChI=1S/C29H29F3N8O.CH4O3S/c1-19-26(38-28-34-9-7-25(37-28)21-4-3-8-33-16-21)15-23(17-35-19)36-27(41)20-5-6-22(24(14-20)29(30,31)32)18-40-12-10-39(2)11-13-40;1-5(2,3)4/h3-9,14-17H,10-13,18H2,1-2H3,(H,36,41)(H,34,37,38);1H3,(H,2,3,4)

HIDE SMILES / InChI
Molecular Formula C29H29F3N8O
Molecular Weight 562.5888
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula CH4O3S
Molecular Weight 96.106
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/20478851 | http://adisinsight.springer.com/drugs/800035564

Flumatinib (HHGV678) is an orally bioavailable antineoplastic tyrosine kinase inhibitor. Flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. Flumatinib was extensively metabolized after oral administration, and the major metabolic pathways observed were amide hydrolysis, demethylation, oxidation, and glucuronide conjugation. It is in phase III clinical trials for the treatment of Chronic myeloid leukemia (in China).

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 1.2 nM [IC50]
Inhibitor
8504
 308.0 nM [IC50]
Inhibitor
8504
 665.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
61.9 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/36814813/
600 mg 1 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FLUMATINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
50.7 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
132 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
27.2 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESMETHYL FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
54.7 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESMETHYL FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
777.4 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/36814813/
600 mg 1 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FLUMATINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
847 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1277 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
243 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESMETHYL FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
390 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESMETHYL FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
16 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/36814813/
600 mg 1 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FLUMATINIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
15.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
22.8 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESMETHYL FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
24.4 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/32757049/
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESMETHYL FLUMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
Doses

Doses

DosePopulationAdverse events​
1200 mg single, oral
Highest studied dose
Dose: 1200 mg
Route: oral
Route: single
Dose: 1200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
DLT: Diarrhea...
Dose limiting toxicities:
Diarrhea (grade 3)
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
600 mg 1 times / day multiple, oral
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
Disc. AE: Thrombocytopenia, Alanine aminotransferase increased...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (grade 3-4, 24%)
Alanine aminotransferase increased (grade 3-4, 5%)
Diarrhea (2%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
800 mg single, oral
Studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
DLT: Diarrhea...
Dose limiting toxicities:
Diarrhea (grade 3)
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
AEs

AEs

AESignificanceDosePopulation
Diarrhea grade 3
DLT
1200 mg single, oral
Highest studied dose
Dose: 1200 mg
Route: oral
Route: single
Dose: 1200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
Diarrhea 2%
Disc. AE
600 mg 1 times / day multiple, oral
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
Thrombocytopenia grade 3-4, 24%
Disc. AE
600 mg 1 times / day multiple, oral
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
Alanine aminotransferase increased grade 3-4, 5%
Disc. AE
600 mg 1 times / day multiple, oral
Studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
Diarrhea grade 3
DLT
800 mg single, oral
Studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/32928796/
PubMed

PubMed

TitleDatePubMed
Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants.
2014-01
[Effect of flumatinib mesylate on C-MYC, HIF-1α and VEGF in U226 line].
2013-12
HH-GV-678, a novel selective inhibitor of Bcr-Abl, outperforms imatinib and effectively overrides imatinib resistance.
2010-10
Patents

Patents

20080312251
2
8183242
2
CN1972917 B
2
US8183242 B2
2

Sample Use Guides

In Vivo Use Guide
400 mg once daily or 600 mg once daily
Route of Administration: Oral
In Vitro Use Guide
Flumatinib of 10.0 micromol/L induced cell apoptosis of 40.06% and 33.32% in K562R and 32Dp210(T315I) cell lines
Substance Class Chemical
Created
by admin
on Mon Mar 31 21:30:33 GMT 2025
Edited
by admin
on Mon Mar 31 21:30:33 GMT 2025
Record UNII
95Y8L63NBC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BENZAMIDE, 4-((4-METHYL-1-PIPERAZINYL)METHYL)-N-(6-METHYL-5-((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINO)-3-PYRIDINYL)-3-(TRIFLUOROMETHYL)-, METHANESULFONATE (1:1)
Preferred Name English
FLUMATINIB MESYLATE
Common Name English
Flumatinib mesylate [WHO-DD]
Common Name English
BENZAMIDE, 4-((4-METHYL-1-PIPERAZINYL)METHYL)-N-(6-METHYL-5-((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINO)-3-PYRIDINYL)-3-(TRIFLUOROMETHYL)-, MONOMETHANESULFONATE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
NCI_THESAURUS C1967
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
Code System Code Type Description
SMS_ID
300000045109
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
FDA UNII
95Y8L63NBC
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
CAS
895519-91-2
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
DRUG BANK
DBSALT002102
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
PUBCHEM
46910592
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
NCI_THESAURUS
C117723
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
EPA CompTox
DTXSID70237780
Created by admin on Mon Mar 31 21:30:33 GMT 2025 , Edited by admin on Mon Mar 31 21:30:33 GMT 2025
PRIMARY
NIH
NCATS
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