Masitinib

Summary

Masitinib (CHEMBL1908391) is a phase-3 clinical-stage small-molecule tyrosine kinase inhibitor (ATC L01EX06) targeting PDGFRA, PDGFRB, and KIT; indicated across 17 conditions including neoplasm and chronic progressive multiple sclerosis.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: L01EX06
• Targets: 3 (PDGFRA, PDGFRB, KIT)
• Indications: 17 conditions
• Clinical trials: 35
• Chemistry: 498.6 Da · C28H30N6OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1908391
Name	Masitinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	10074640
ChEBI	CHEBI:63450
ATC	L01EX06
Molecular formula	C28H30N6OS
Molecular weight	498.6
InChIKey	WJEOLQLKVOPQFV-UHFFFAOYSA-N

SMILES: CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC(=CS4)C5=CN=CC=C5

IUPAC name: 4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide

ChEBI definition: A member of the class of benzamides that is the carboxamide resulting from the formal condensation of the carboxy group of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid with the primary amino group of 4-methyl-N3-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]benzene-1,3-diamine. It is a highly selective oral tyrosine kinase inhibitor.

Pharmacological roles (ChEBI): tyrosine kinase inhibitor, antineoplastic agent, antirheumatic drug.

Also known as: Kinavet, Masitinib, AB-1010, SID124950163, masitinib, SID99460877, MASITINIB, MASITINIB (AB1010), Masitinib (AB1010)

Parent form; salt/anhydrous children: CHEMBL5315058

Patent coverage: 1,195 distinct patent families (2,808 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 2,430 (87%) 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
PDGFRA	platelet derived growth factor receptor alpha	Inhibition	6.27	6.2%	P16234
PDGFRB	platelet derived growth factor receptor beta	Inhibition	6.1	2.3%	P09619
KIT	KIT proto-oncogene, receptor tyrosine kinase	Inhibition	6.7	0.5%	P10721

Broader ChEMBL bioactivity targets: 31 (assay-derived). Sample: Receptor tyrosine-protein kinase erbB-2, Tyrosine-protein kinase Fyn, Macrophage colony-stimulating factor 1 receptor, Tyrosine-protein kinase ABL1, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Platelet-derived growth factor receptor alpha, Epidermal growth factor receptor, Tyrosine-protein kinase Yes, Serine/threonine-protein kinase pim-1.

Bioactivity

ChEMBL activities: 66 potent at pChembl ≥ 5 of 66 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ABL1	8.68	Kd	2.1	nM	CHEMBL_ACT_7581195
ABL1	8.34	Kd	4.6	nM	CHEMBL_ACT_7581191
KIT	8.33	Kd	4.7	nM	CHEMBL_ACT_7580993
KIT	8.24	Kd	5.8	nM	CHEMBL_ACT_7580991
SLC25A6	8.22	Kd	6	nM	CHEMBL_ACT_17938958
ABL1	8.22	Kd	6	nM	CHEMBL_ACT_7581190
CSF1R	8.12	Kd	7.6	nM	CHEMBL_ACT_7581199
KIT	8.1	Kd	7.9	nM	CHEMBL_ACT_7580990
ABL1	8.1	Kd	8	nM	CHEMBL_ACT_7581183
KIT	8.09	Kd	8.1	nM	CHEMBL_ACT_7580986
PDGFRB	8.08	Kd	8.4	nM	CHEMBL_ACT_7581076
DDR1	8.06	Kd	8.7	nM	CHEMBL_ACT_7581051
ABL1	8	Kd	10	nM	CHEMBL_ACT_7581185
ABL1	7.96	Kd	11	nM	CHEMBL_ACT_7581187
KIT	7.92	Kd	12	nM	CHEMBL_ACT_7580987
ACOX1	7.85	Kd	14	nM	CHEMBL_ACT_17879599
ABL1	7.6	Kd	25	nM	CHEMBL_ACT_7581194
PDGFRA	7.6	Kd	25	nM	CHEMBL_ACT_7581238
DDR2	7.58	Kd	26	nM	CHEMBL_ACT_7580977
LCK	7.51	Kd	31	nM	CHEMBL_ACT_7581217
ABL1	7.26	Kd	55	nM	CHEMBL_ACT_7581196
LYN	7.21	Kd	61	nM	CHEMBL_ACT_7581063
BCR	7.11	Kd	78	nM	CHEMBL_ACT_17884704
ABL1	7.11	Kd	78	nM	CHEMBL_ACT_7581184
FRK	7.06	Kd	87	nM	CHEMBL_ACT_7581056
ABL1	6.96	Kd	110	nM	CHEMBL_ACT_7581186
ABL2	6.96	Kd	110	nM	CHEMBL_ACT_7581197
ABL1	6.85	Kd	140	nM	CHEMBL_ACT_7581182
ABL1	6.85	Kd	140	nM	CHEMBL_ACT_7581188
ABL1	6.85	Kd	140	nM	CHEMBL_ACT_7581189

Target pathways

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

Top Reactome pathways

48 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	3	KIT, PDGFRA, PDGFRB
Constitutive Signaling by Aberrant PI3K in Cancer	3	KIT, PDGFRA, PDGFRB
RAF/MAP kinase cascade	3	KIT, PDGFRA, PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	3	KIT, PDGFRA, PDGFRB
Downstream signal transduction	2	PDGFRA, PDGFRB
Signaling by PDGF	2	PDGFRA, PDGFRB
Developmental Biology	1	KIT
Signaling by SCF-KIT	1	KIT
Regulation of KIT signaling	1	KIT
Signal Transduction	1	KIT
Disease	1	KIT
Negative regulation of the PI3K/AKT network	1	KIT
Generic Transcription Pathway	1	KIT
PI3K/AKT Signaling in Cancer	1	KIT
Diseases of signal transduction by growth factor receptors and second messengers	1	KIT
MAPK family signaling cascades	1	KIT
MAPK1/MAPK3 signaling	1	KIT
RNA Polymerase II Transcription	1	KIT
Gene expression (Transcription)	1	KIT
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
Intracellular signaling by second messengers	1	KIT
Signaling by Receptor Tyrosine Kinases	1	KIT
Dasatinib-resistant KIT mutants	1	KIT
Imatinib-resistant KIT mutants	1	KIT
KIT mutants bind TKIs	1	KIT
Masitinib-resistant KIT mutants	1	KIT
Nilotinib-resistant KIT mutants	1	KIT
Regorafenib-resistant KIT mutants	1	KIT
Signaling by kinase domain mutants of KIT	1	KIT

Dominant GO biological processes

GO term	Targets
cell surface receptor protein tyrosine kinase signaling pathway	3
positive regulation of cell population proliferation	3
cell migration	3
positive regulation of cell migration	3
protein autophosphorylation	3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3
cell chemotaxis	3
protein phosphorylation	3
chemotaxis	3
hematopoietic progenitor cell differentiation	2
peptidyl-tyrosine phosphorylation	2
regulation of actin cytoskeleton organization	2
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	2
platelet-derived growth factor receptor signaling pathway	2
positive regulation of calcium-mediated signaling	2

Indications & clinical

Indications

17 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
neoplasm	4	MONDO:0005070	EFO:0000616
chronic progressive multiple sclerosis	3	MONDO:0005284	EFO:0003840
plasma cell myeloma	3	MONDO:0009693	EFO:0001378
metastatic melanoma	3	MONDO:0005191	EFO:0002617
exocrine pancreatic carcinoma	3	MONDO:0005192	EFO:0002618
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
amyotrophic lateral sclerosis	3	MONDO:0004976	MONDO:0004976
asthma	3	MONDO:0004979	MONDO:0004979
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
gastrointestinal stromal tumor	3	MONDO:0011719	MONDO:0011719
rheumatoid arthritis	2	MONDO:0008383	EFO:0000685
psoriasis	2	MONDO:0005083	EFO:0000676
mastocytosis	2	MONDO:0007950	EFO:0009001
ovarian cancer	2	MONDO:0008170	MONDO:0008170
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 35.

Phase distribution

Phase	Trials
PHASE3	19
PHASE2	12
PHASE2/PHASE3	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT05564169	PHASE3	NOT_YET_RECRUITING	Masitinib in Patients With Mild Alzheimer’s Disease
NCT07174492	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients
NCT00789633	PHASE3	COMPLETED	Masitinib in Combination With Gemcitabine for Treatment of Patients With Advanced/Metastatic Pancreatic Cancer
NCT00812240	PHASE3	TERMINATED	Masitinib in First Line Treatment of Gastro-Intestinal Stromal Tumor (GIST)
NCT00814073	PHASE3	COMPLETED	Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis
NCT01280565	PHASE3	TERMINATED	Masitinib in Non-Resectable or Metastatic Stage 3/4 Melanoma Carrying a Mutation in the Juxta Membrane Domain of c-Kit
NCT01410695	PHASE2/PHASE3	TERMINATED	Masitinib in Refractory Active Rheumatoid Arthritis
NCT01433497	PHASE3	COMPLETED	Efficacy and Safety of Masitinib in the Treatment of Progressive Multiple Sclerosis
NCT01449162	PHASE3	COMPLETED	Masitinib in Treatment of Patients With Severe Persistent Asthma Treated With Oral Corticosteroids
NCT01470131	PHASE3	TERMINATED	A Phase 3 Study to Evaluate Efficacy and Safety of Masitinib in Patients With Relapse or Refractory Multiple Myeloma
NCT01694277	PHASE3	COMPLETED	Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib
NCT01872598	PHASE3	COMPLETED	Masitinib in Patients With Mild to Moderate Alzheimer’s Disease
NCT02009423	PHASE3	TERMINATED	Masitinib in Patients With Localized, Primary GIST After Complete Surgery and With High Risk of Recurrence
NCT02490488	PHASE2/PHASE3	COMPLETED	Masitinib in Combination With Gemcitabine in Advanced/Metastatic Epithelial Ovarian Cancer Patients
NCT02588677	PHASE2/PHASE3	COMPLETED	Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)
NCT02605044	PHASE3	TERMINATED	Masitinib in Combination With FOLFIRI for Second-line Treatment of Patients With Metastatic Colorectal Cancer
NCT03556956	PHASE2/PHASE3	COMPLETED	Masitinib in Combination With FOLFIRI in Third or Fourth Line of Treatment of Patients With Metastatic Colorectal Cancer
NCT03761225	PHASE3	COMPLETED	Masitinib Plus Docetaxel in Metastatic Castration-resistant Prostate Cancer
NCT03766295	PHASE3	COMPLETED	Masitinib Plus Gemcitabine in Pancreatic Cancer
NCT03771040	PHASE3	COMPLETED	Masitinib in the Treatment of Patients With Severe Uncontrolled Asthma and Elevated Eosinophil Levels
NCT04333108	PHASE3	UNKNOWN	Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
NCT05441488	PHASE3	SUSPENDED	Masitinib in the Treatment of Patients With Primary Progressive or Non-active Secondary Progressive Multiple Sclerosis
NCT00831922	PHASE2	COMPLETED	Efficacy of Oral AB1010 in Adult Patients With Active Rheumatoid Arthritis
NCT00831974	PHASE2	COMPLETED	Efficacy of AB1010 in Patients With Systemic Indolent Mastocytosis
NCT00866138	PHASE2	COMPLETED	Masitinib in Relapse or Refractory Multiple Myeloma With t(4/14) Translocation Expressing or Not FGFR3
NCT00913432	PHASE2	COMPLETED	Masitinib in Combination With Methotrexate, in Treatment of Patients With Active Rheumatoid Arthritis
NCT00976118	PHASE2	COMPLETED	Activity of Masitinib (AB1010) in Mild to Moderate Alzheimer’s Disease
NCT00998751	PHASE2	COMPLETED	Masitinib in Locally Advanced/Metastatic Gastro-intestinal Stromal Tumour (GIST)
NCT01045577	PHASE2	COMPLETED	A Double-blind, Placebo-controlled, Randomized, Parallel-group Study to Evaluate the Activity of Oral AB1010 in Adults Patients With Moderate to Severe Chronic Plaque Psoriasis
NCT01266369	PHASE2	COMPLETED	Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation
NCT01450488	PHASE2	COMPLETED	Masitinib in Primary Progressive Multiple Sclerosis or Relapse-free Secondary Progressive Multiple Sclerosis
NCT01506336	PHASE2	COMPLETED	Masitinib in Patients With Gastro-Intestinal Stromal Tumour Resistant to Imatinib
NCT04622865	PHASE2	UNKNOWN	Masitinib Combined With Isoquercetin and Best Supportive Care in Hospitalized Patients With Moderate and Severe COVID-19
NCT05449444	PHASE2	UNKNOWN	Masitinib for the Treatment of Severe Mast Cell Activation Syndrome

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

121 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
AXITINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
BOSUTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
DASATINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
ERLOTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
FEDRATINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
LENVATINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
NILOTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
NINTEDANIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
PONATINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
QUIZARTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
SORAFENIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
SUNITINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
TIVOZANIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
VANDETANIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA, PDGFRB
BARASERTIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
BRIVANIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
CANERTINIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
CEDIRANIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
DOVITINIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
LESTAURTINIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
LINIFANIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
MOTESANIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
SARACATINIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
SEMAXANIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
VATALANIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
VIMSELTINIB	ChEMBL	Phase 3	KIT, PDGFRA, PDGFRB
CENISERTIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
DEFOSBARASERTIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
DORAMAPIMOD	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
FORETINIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
ILORASERTIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
R-406	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
RAF-265	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
SOTULETINIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
SU-014813	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
TANDUTINIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
TOZASERTIB	ChEMBL	Phase 2	KIT, PDGFRA, PDGFRB
Afatinib	PubChem	Approved	KIT, PDGFRA, PDGFRB
Idelalisib	PubChem	Approved	KIT, PDGFRA, PDGFRB
Selumetinib	PubChem	Approved	KIT, PDGFRA, PDGFRB
AVAPRITINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT, PDGFRA
Gefitinib	ChEMBL + PubChem	Phase 4 (approved)	KIT, PDGFRA
CERITINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA
INFIGRATINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA
NINTEDANIB ESYLATE	ChEMBL	Phase 4 (approved)	PDGFRA, PDGFRB
RIPRETINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRA
ALVOCIDIB	ChEMBL	Phase 3	KIT, PDGFRA
CRENOLANIB	ChEMBL	Phase 3	PDGFRA, PDGFRB
ENZASTAURIN	ChEMBL	Phase 3	KIT, PDGFRB
FAMITINIB	ChEMBL	Phase 3	KIT, PDGFRB
FLUMATINIB	ChEMBL	Phase 3	KIT, PDGFRB
PIMICOTINIB	ChEMBL	Phase 3	KIT, PDGFRA
RUBOXISTAURIN	ChEMBL	Phase 3	KIT, PDGFRB
AMUVATINIB	ChEMBL	Phase 2	KIT, PDGFRA