Bezuclastinib

Summary

Bezuclastinib (CHEMBL5095229) is a phase-3 clinical-stage small molecule targeting KIT; indicated across 3 conditions including neoplasm and gastrointestinal stromal tumor.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (KIT)
• Indications: 3 conditions
• Clinical trials: 5
• Chemistry: 331.4 Da · C19H17N5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5095229
Name	Bezuclastinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	75593308
Molecular formula	C19H17N5O
Molecular weight	331.4
InChIKey	NVSHVYGIYPBTEZ-UHFFFAOYSA-N

SMILES: CC1=C(NN=C1C(=O)NC2=CN=C3C(=C2)C=C(N3)C4=CC=CC=C4)C

IUPAC name: 4,5-dimethyl-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazole-3-carboxamide

Also known as: Bezuclastinib, CGT-9486, CGT9486, Plx-9486, Plx9486, PLX9486, BEZUCLASTINIB

Patent coverage: 126 distinct patent families (438 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 373 (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
KIT	KIT proto-oncogene, receptor tyrosine kinase	Inhibition	7.55	0.5%	P10721

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Mast/stem cell growth factor receptor Kit.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
KIT	5.26	Ki	5500	nM	CHEMBL_ACT_27624476

Target pathways

Aggregated over 1 target gene(s): KIT.

Top Reactome pathways

39 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	1	KIT
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
Constitutive Signaling by Aberrant PI3K in Cancer	1	KIT
Diseases of signal transduction by growth factor receptors and second messengers	1	KIT
RAF/MAP kinase cascade	1	KIT
MAPK family signaling cascades	1	KIT
MAPK1/MAPK3 signaling	1	KIT
PI5P, PP2A and IER3 Regulate PI3K/AKT 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
Sunitinib-resistant KIT mutants	1	KIT
Signaling by juxtamembrane domain KIT mutants	1	KIT

Dominant GO biological processes

GO term	Targets
ovarian follicle development	1
hematopoietic progenitor cell differentiation	1
myeloid progenitor cell differentiation	1
lymphoid progenitor cell differentiation	1
immature B cell differentiation	1
mast cell chemotaxis	1
positive regulation of dendritic cell cytokine production	1
glycosphingolipid metabolic process	1
inflammatory response	1
signal transduction	1
spermatogenesis	1
spermatid development	1
positive regulation of cell population proliferation	1
primordial germ cell migration	1
regulation of cell shape	1

Indications & clinical

Indications

3 indications (0 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	1	MONDO:0005070	EFO:0000616
gastrointestinal stromal tumor	1	MONDO:0011719	MONDO:0011719

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

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
Not specified	2
PHASE3	1
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05208047	PHASE3	ACTIVE_NOT_RECRUITING	(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
NCT04996875	PHASE2	RECRUITING	(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis
NCT02401815	PHASE1/PHASE2	COMPLETED	CGT9486 (Formerly Known as PLX9486) as a Single Agent and in Combination With PLX3397 (Pexidartinib) or Sunitinib in Participants With Advanced Solid Tumors
NCT06915766	Not specified	AVAILABLE	Expanded Access to Bezuclastinib for Patients With NonAdvanced Systemic Mastocytosis or Advanced Systemic Mastocytosis
NCT06948955	Not specified	AVAILABLE	Expanded Access to Bezuclastinib to be Coadministered With Sunitinib for Patients With Gastrointestinal Stromal Tumors

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.

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

Molecule	Source	Status	Shared targets
AVAPRITINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	KIT
AXITINIB	ChEMBL	Phase 4 (approved)	KIT
BOSUTINIB	ChEMBL	Phase 4 (approved)	KIT
BRIGATINIB	ChEMBL	Phase 4 (approved)	KIT
CABOZANTINIB	ChEMBL	Phase 4 (approved)	KIT
CERITINIB	ChEMBL	Phase 4 (approved)	KIT
DASATINIB	ChEMBL	Phase 4 (approved)	KIT
ENTRECTINIB	ChEMBL	Phase 4 (approved)	KIT
ERLOTINIB	ChEMBL	Phase 4 (approved)	KIT
FEDRATINIB	ChEMBL	Phase 4 (approved)	KIT
INFIGRATINIB	ChEMBL	Phase 4 (approved)	KIT
LENVATINIB	ChEMBL	Phase 4 (approved)	KIT
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	KIT
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	KIT
NILOTINIB	ChEMBL	Phase 4 (approved)	KIT
NINTEDANIB	ChEMBL	Phase 4 (approved)	KIT
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	KIT
PONATINIB	ChEMBL	Phase 4 (approved)	KIT
QUIZARTINIB	ChEMBL	Phase 4 (approved)	KIT
RIPRETINIB	ChEMBL	Phase 4 (approved)	KIT
RUXOLITINIB	ChEMBL	Phase 4 (approved)	KIT
SORAFENIB	ChEMBL	Phase 4 (approved)	KIT
SUNITINIB	ChEMBL	Phase 4 (approved)	KIT
TIVOZANIB	ChEMBL	Phase 4 (approved)	KIT
VANDETANIB	ChEMBL	Phase 4 (approved)	KIT
ALVOCIDIB	ChEMBL	Phase 3	KIT
BARASERTIB	ChEMBL	Phase 3	KIT
BRIVANIB	ChEMBL	Phase 3	KIT
CANERTINIB	ChEMBL	Phase 3	KIT
CEDIRANIB	ChEMBL	Phase 3	KIT
DOVITINIB	ChEMBL	Phase 3	KIT
ENZASTAURIN	ChEMBL	Phase 3	KIT
FAMITINIB	ChEMBL	Phase 3	KIT
FLUMATINIB	ChEMBL	Phase 3	KIT
LESTAURTINIB	ChEMBL	Phase 3	KIT
LINIFANIB	ChEMBL	Phase 3	KIT
MASITINIB	ChEMBL	Phase 3	KIT
MOTESANIB	ChEMBL	Phase 3	KIT
PIMICOTINIB	ChEMBL	Phase 3	KIT
RUBOXISTAURIN	ChEMBL	Phase 3	KIT
SARACATINIB	ChEMBL	Phase 3	KIT
SEMAXANIB	ChEMBL	Phase 3	KIT
SITRAVATINIB	ChEMBL	Phase 3	KIT
VATALANIB	ChEMBL	Phase 3	KIT
VIMSELTINIB	ChEMBL	Phase 3	KIT
AMUVATINIB	ChEMBL	Phase 2	KIT
BAY-1161909	ChEMBL	Phase 2	KIT
BEMCENTINIB	ChEMBL	Phase 2	KIT
BERZOSERTIB	ChEMBL	Phase 2	KIT
BFH-772	ChEMBL	Phase 2	KIT
BMS-777607	ChEMBL	Phase 2	KIT
CENISERTIB	ChEMBL	Phase 2	KIT
CEP-32496	ChEMBL	Phase 2	KIT
DANUSERTIB	ChEMBL	Phase 2	KIT
DATELLIPTIUM	ChEMBL	Phase 2	KIT