FLUMBATINIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H29F3N8O
Molecular Weight	562.5888
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN1CCN(CC2=CC=C(C=C2C(F)(F)F)C(=O)NC3=CC(NC4=NC=CC(=N4)C5=CC=CN=C5)=C(C)N=C3)CC1

InChI

InChIKey=BJCJYEYYYGBROF-UHFFFAOYSA-N

InChI=1S/C29H29F3N8O/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/h3-9,14-17H,10-13,18H2,1-2H3,(H,36,41)(H,34,37,38)

HIDE SMILES / InChI

Description

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

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase ABL 29	Inhibitor 8,504	1.2 nM [IC50]
Platelet-derived growth factor receptor beta 56	Inhibitor 8,504	308.0 nM [IC50]
Stem cell growth factor receptor 57	Inhibitor 8,504	665.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic myeloid leukemia 24	Primary		Phase III 665	Unknown

C_max

Value	Dose	Analyte	Population
61.9 ng/mL	600 mg 1 times / day multiple, oral	FLUMATINIB serum	Homo sapiens
50.7 ng/mL	400 mg single, oral	FLUMATINIB plasma	Homo sapiens
132 ng/mL	400 mg single, oral	FLUMATINIB plasma	Homo sapiens
27.2 ng/mL	400 mg single, oral	N-DESMETHYL FLUMATINIB plasma	Homo sapiens
54.7 ng/mL	400 mg single, oral	N-DESMETHYL FLUMATINIB plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
777.4 ng × h/mL	600 mg 1 times / day multiple, oral	FLUMATINIB serum	Homo sapiens
847 ng × h/mL	400 mg single, oral	FLUMATINIB plasma	Homo sapiens
1277 ng × h/mL	400 mg single, oral	FLUMATINIB plasma	Homo sapiens
243 ng × h/mL	400 mg single, oral	N-DESMETHYL FLUMATINIB plasma	Homo sapiens
390 ng × h/mL	400 mg single, oral	N-DESMETHYL FLUMATINIB plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
16 h	600 mg 1 times / day multiple, oral	FLUMATINIB serum	Homo sapiens
13.3 h	400 mg single, oral	FLUMATINIB plasma	Homo sapiens
15.5 h	400 mg single, oral	FLUMATINIB plasma	Homo sapiens
22.8 h	400 mg single, oral	N-DESMETHYL FLUMATINIB plasma	Homo sapiens
24.4 h	400 mg single, oral	N-DESMETHYL FLUMATINIB plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1200 mg single, oral Highest studied dose	unhealthy, ADULT	DLT: Diarrhea...
600 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT	Disc. AE: Thrombocytopenia, Alanine aminotransferase increased...
800 mg single, oral Studied dose	unhealthy, ADULT	DLT: Diarrhea...

Showing 1 to 3 of 3 entries

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AEs

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AE	Significance	Dose	Population
Diarrhea	grade 3 DLT	1200 mg single, oral Highest studied dose	unhealthy, ADULT
Diarrhea	2% Disc. AE	600 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Thrombocytopenia	grade 3-4, 24% Disc. AE	600 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Alanine aminotransferase increased	grade 3-4, 5% Disc. AE	600 mg 1 times / day multiple, oral Studied dose	unhealthy, ADULT
Diarrhea	grade 3 DLT	800 mg single, oral Studied dose	unhealthy, ADULT

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PubMed

Title	Date	PubMed
No data available in table

Patents

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

Show entries

Name

Type

Language

HH-GV678

Preferred Name

English

FLUMBATINIB

Official Name

English

flumbatinib [INN]

Common Name

English

Flumatinib [WHO-DD]

Common Name

English

4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-(6-METHYL-5-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PYRIDIN-3-YL)-3-TRIFLUOROMETHYL-BENZAMIDE

Systematic Name

English

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Show entries

Classification Tree

Code System

Code

Antineoplastic Protein Inhibitor

NCI_THESAURUS

C129825

Protein Kinase Inhibitor

NCI_THESAURUS

C1967

Showing 1 to 2 of 2 entries

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Show entries

Code System

Code

Type

Description

NCI_THESAURUS

C138991

PRIMARY

PUBCHEM

46848036

PRIMARY

INN

11831

PRIMARY

FDA UNII

R4009Y24AI

PRIMARY

CAS

895519-90-1

PRIMARY

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ACTIVE MOIETY


					R4009Y24AI

FLUMBATINIB

METABOLITE (PARENT)


					8Z0HZM0V8C

4-((4-METHYL-1-PIPERAZINYL)METHYL)-3-(TRIFLUOROMETHYL)BENZOIC ACID

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2