Flumatinib

Summary

Flumatinib (CHEMBL3545413) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting PDGFRB, KIT, and ABL1; indicated across 2 conditions including chronic myeloid leukemia and acute lymphoblastic leukemia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (PDGFRB, KIT, ABL1)
• Indications: 2 conditions
• Clinical trials: 10
• Chemistry: 562.6 Da · C29H29F3N8O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3545413
Name	Flumatinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	46848036
ChEBI	CHEBI:233593
Molecular formula	C29H29F3N8O
Molecular weight	562.6
InChIKey	BJCJYEYYYGBROF-UHFFFAOYSA-N

SMILES: CC1=C(C=C(C=N1)NC(=O)C2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)NC4=NC=CC(=N4)C5=CN=CC=C5

IUPAC name: 4-[(4-methylpiperazin-1-yl)methyl]-N-[6-methyl-5-[(4-pyridin-3-ylpyrimidin-2-yl)amino]-3-pyridinyl]-3-(trifluoromethyl)benzamide

ChEBI definition: A secondary carboxamide resulting from the formal condensation of the carboxy group of 4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzoic acid with the amino group of 2-methyl-N3-[4-(pyridin-3-yl)pyrimidin-2-yl]pyridine-3,5-diamine. It is an inhibitor of the non-receptor tyrosine kinase Bcr-Abl (IC50 = 1.2 nM) and has been approved in China for the treatment of chronic myeloid leukaemia.

Pharmacological roles (ChEBI): antineoplastic agent, apoptosis inducer, EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor.

Also known as: Flumatinib, Flumbatinib, HH-GV678, Hhgv-678, FLUMATINIB, Flumatinib (mesylate)

Parent form; salt/anhydrous children: CHEMBL3901539

Patent coverage: 123 distinct patent families (254 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 217 (85%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PDGFRB	platelet derived growth factor receptor beta	Inhibition	6.51	2.3%	P09619
KIT	KIT proto-oncogene, receptor tyrosine kinase	Inhibition	6.18	0.5%	P10721
ABL1	ABL proto-oncogene 1, non-receptor tyrosine kinase	Inhibition	8.92	1.2%	P00519

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Bcr/Abl fusion protein.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 12 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ABL1	8.92	IC50	1.2	nM	CHEMBL_ACT_24707073
ABL1	8.21	IC50	6.2	nM	CHEMBL_ACT_19289514
ABL1	7.98	IC50	10.4	nM	CHEMBL_ACT_19289502
ABL1	7.87	IC50	13.6	nM	CHEMBL_ACT_19289496
ABL1	7.76	IC50	17.4	nM	CHEMBL_ACT_19289499
ABL1	7.74	IC50	18.1	nM	CHEMBL_ACT_19289511
ABL1	7.66	IC50	21.7	nM	CHEMBL_ACT_19289493
ABL1	7.22	IC50	60.1	nM	CHEMBL_ACT_19289490
ABL1	6.95	IC50	113.1	nM	CHEMBL_ACT_19289505
PDGFRB	6.51	IC50	307.6	nM	CHEMBL_ACT_24707074
ABL1	6.5	IC50	318.4	nM	CHEMBL_ACT_19289508
KIT	6.18	IC50	665.5	nM	CHEMBL_ACT_24707075

Target pathways

Aggregated over 3 target gene(s): PDGFRB, KIT, ABL1.

Top Reactome pathways

88 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	2	KIT, PDGFRB
Developmental Biology	2	ABL1, KIT
Signal Transduction	2	ABL1, KIT
Disease	2	ABL1, KIT
Generic Transcription Pathway	2	ABL1, KIT
Constitutive Signaling by Aberrant PI3K in Cancer	2	KIT, PDGFRB
RAF/MAP kinase cascade	2	KIT, PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	KIT, PDGFRB
RNA Polymerase II Transcription	2	ABL1, KIT
Gene expression (Transcription)	2	ABL1, KIT
Hemostasis	1	ABL1
Signaling by SCF-KIT	1	KIT
Regulation of KIT signaling	1	KIT
Cell Cycle	1	ABL1
Innate Immune System	1	ABL1
Immune System	1	ABL1
Downstream signal transduction	1	PDGFRB
Signaling by PDGF	1	PDGFRB
Signaling by Rho GTPases	1	ABL1
RHO GTPase Effectors	1	ABL1
Negative regulation of the PI3K/AKT network	1	KIT
Fcgamma receptor (FCGR) dependent phagocytosis	1	ABL1
Regulation of actin dynamics for phagocytic cup formation	1	ABL1
Epigenetic regulation of gene expression	1	ABL1
PI3K/AKT Signaling in Cancer	1	KIT
Signaling by ROBO receptors	1	ABL1
Axon guidance	1	ABL1
Role of ABL in ROBO-SLIT signaling	1	ABL1
Mitotic G1 phase and G1/S transition	1	ABL1
Myogenesis	1	ABL1
Diseases of signal transduction by growth factor receptors and second messengers	1	KIT
Infectious disease	1	ABL1
RHO GTPases Activate WASPs and WAVEs	1	ABL1
MAPK family signaling cascades	1	KIT
MAPK1/MAPK3 signaling	1	KIT
HDR through Single Strand Annealing (SSA)	1	ABL1
DNA Double-Strand Break Repair	1	ABL1
Homology Directed Repair	1	ABL1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	ABL1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	ABL1
DNA Double Strand Break Response	1	ABL1
Cyclin D associated events in G1	1	ABL1
G1 Phase	1	ABL1
Cell Cycle, Mitotic	1	ABL1
DNA Repair	1	ABL1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	KIT
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	KIT
Transcriptional regulation by RUNX2	1	ABL1
Transcriptional regulation by RUNX1	1	ABL1
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	ABL1

Dominant GO biological processes

GO term	Targets
protein phosphorylation	3
signal transduction	2
cell surface receptor protein tyrosine kinase signaling pathway	2
positive regulation of cell population proliferation	2
positive regulation of cell migration	2
regulation of actin cytoskeleton organization	2
platelet-derived growth factor receptor-beta signaling pathway	2
protein autophosphorylation	2
platelet-derived growth factor receptor signaling pathway	2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
cell chemotaxis	2
positive regulation of ERK1 and ERK2 cascade	2
chemotaxis	2
cell migration	2
actin cytoskeleton organization	2

Indications & clinical

Indications

2 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
chronic myeloid leukemia	3	MONDO:0011996	EFO:0000339
acute lymphoblastic leukemia	3	MONDO:0004967	EFO:0000220

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE4	4
PHASE2	2
Not specified	2
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05367765	PHASE4	NOT_YET_RECRUITING	A Real World Study of the Efficacy and Safety of Flumatinib Versus Imatinib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase
NCT04677439	PHASE4	UNKNOWN	Flumatinib in CML-CP Patients With Ph+ Post Imatinib Failure
NCT04933526	PHASE4	UNKNOWN	The Efficacy and Safety of Switching to Flumatinib Versus Dasatinib After Imatinib-related Low-grade Adverse Events in CML-CP Patients
NCT05071482	PHASE4	TERMINATED	Flumatinib Versus Imatinib Combined With Chemotherapy for de Novo Ph+ ALL
NCT04375683	PHASE3	UNKNOWN	Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in Ph Positive ALL
NCT01503502	PHASE2	UNKNOWN	A Phase II Study of Flumatinib Versus Imatinib to Treat Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
NCT05433532	PHASE2	COMPLETED	Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients
NCT06530810	PHASE1	NOT_YET_RECRUITING	Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML)
NCT04681820	Not specified	UNKNOWN	Evaluating Efficacy and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning,Failure) to Imatinib or Dasatinib
NCT04739826	Not specified	UNKNOWN	Flumatinib Versus Nilotinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

150 molecules share ≥1 primary target. Top 100 by shared-target count:

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	ABL1, KIT, PDGFRB
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	ABL1, KIT, PDGFRB
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	ABL1, KIT, PDGFRB
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	ABL1, KIT, PDGFRB
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	ABL1, KIT, PDGFRB
AXITINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
BOSUTINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
DASATINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
ERLOTINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
FEDRATINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
LENVATINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
NILOTINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
NINTEDANIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
PONATINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
QUIZARTINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
SORAFENIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
SUNITINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
TIVOZANIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
VANDETANIB	ChEMBL	Phase 4 (approved)	ABL1, KIT, PDGFRB
BRIVANIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
CANERTINIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
CEDIRANIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
DOVITINIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
LESTAURTINIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
LINIFANIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
MASITINIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
MOTESANIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
SARACATINIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
SEMAXANIB	ChEMBL	Phase 3	ABL1, KIT, PDGFRB
CENISERTIB	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
CEP-32496	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
DEFOSBARASERTIB	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
DORAMAPIMOD	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
FORETINIB	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
ILORASERTIB	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
MILCICLIB	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
R-406	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
RAF-265	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
SU-014813	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
TOZASERTIB	ChEMBL	Phase 2	ABL1, KIT, PDGFRB
Idelalisib	PubChem	Approved	ABL1, KIT, PDGFRB
Selumetinib	PubChem	Approved	ABL1, KIT, PDGFRB
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	ABL1, KIT
BRIGATINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT
CABOZANTINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT
CERITINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT
ENTRECTINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT
INFIGRATINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT
LAPATINIB	ChEMBL	Phase 4 (approved)	ABL1, PDGFRB
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRB
RUXOLITINIB	ChEMBL	Phase 4 (approved)	ABL1, KIT
TOVORAFENIB	ChEMBL	Phase 4 (approved)	ABL1, PDGFRB
ALVOCIDIB	ChEMBL	Phase 3	ABL1, KIT
BARASERTIB	ChEMBL	Phase 3	KIT, PDGFRB
ENZASTAURIN	ChEMBL	Phase 3	KIT, PDGFRB
FAMITINIB	ChEMBL	Phase 3	KIT, PDGFRB
RUBOXISTAURIN	ChEMBL	Phase 3	KIT, PDGFRB
VATALANIB	ChEMBL	Phase 3	KIT, PDGFRB
VIMSELTINIB	ChEMBL	Phase 3	KIT, PDGFRB
AEE-788	ChEMBL	Phase 2	ABL1, PDGFRB
BAFETINIB	ChEMBL	Phase 2	ABL1, PDGFRB
BERZOSERTIB	ChEMBL	Phase 2	ABL1, KIT
BFH-772	ChEMBL	Phase 2	KIT, PDGFRB
BMS-777607	ChEMBL	Phase 2	ABL1, KIT
DANUSERTIB	ChEMBL	Phase 2	ABL1, KIT
ENMD-2076	ChEMBL	Phase 2	ABL1, KIT
GLESATINIB	ChEMBL	Phase 2	ABL1, PDGFRB
GOLVATINIB	ChEMBL	Phase 2	ABL1, PDGFRB
MK-2461	ChEMBL	Phase 2	ABL1, PDGFRB
NARAZACICLIB	ChEMBL	Phase 2	ABL1, PDGFRB
NEFLAMAPIMOD	ChEMBL	Phase 2	ABL1, PDGFRB
OSI-632	ChEMBL	Phase 2	ABL1, PDGFRB
REBASTINIB	ChEMBL	Phase 2	ABL1, KIT
RISVODETINIB	ChEMBL	Phase 2	ABL1, KIT
SOTRASTAURIN	ChEMBL	Phase 2	ABL1, PDGFRB
SOTULETINIB	ChEMBL	Phase 2	KIT, PDGFRB
TANDUTINIB	ChEMBL	Phase 2	KIT, PDGFRB
TELATINIB	ChEMBL	Phase 2	KIT, PDGFRB
TG100-801	ChEMBL	Phase 2	ABL1, PDGFRB
Binimetinib	PubChem	Approved	ABL1, PDGFRB
dacomitinib	PubChem	Approved	ABL1, PDGFRB
Fostamatinib	PubChem	Approved	ABL1, PDGFRB
Trametinib	PubChem	Approved	ABL1, PDGFRB
AVAPRITINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	ABL1
ASCIMINIB	ChEMBL	Phase 4 (approved)	ABL1
BIOTIN	ChEMBL	Phase 4 (approved)	ABL1
DABRAFENIB	ChEMBL	Phase 4 (approved)	ABL1
FILGOTINIB	ChEMBL	Phase 4 (approved)	ABL1
GILTERITINIB	ChEMBL	Phase 4 (approved)	PDGFRB
IBRUTINIB	ChEMBL	Phase 4 (approved)	ABL1
MEBENDAZOLE	ChEMBL	Phase 4 (approved)	ABL1
NERATINIB	ChEMBL	Phase 4 (approved)	ABL1
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	KIT
NINTEDANIB ESYLATE	ChEMBL	Phase 4 (approved)	PDGFRB
PACRITINIB	ChEMBL	Phase 4 (approved)	PDGFRB
RIPRETINIB	ChEMBL	Phase 4 (approved)	KIT
SUNITINIB MALATE	ChEMBL	Phase 4 (approved)	PDGFRB
TIRBANIBULIN	ChEMBL	Phase 4 (approved)	ABL1