Avapritinib

Summary

Avapritinib (CHEMBL4204794) is an approved small molecule (ATC L01EX18) targeting KIT; indicated across 7 conditions including neoplasm and gastrointestinal stromal tumor; with CIViC clinical evidence for 3 variant-indication associations (e.g. KIT D816V in systemic mastocytosis).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EX18
• Targets: 1 (KIT)
• Indications: 7 conditions
• Clinical trials: 22
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 498.6 Da · C26H27FN10

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4204794
Name	Avapritinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	118023034
ATC	L01EX18
Molecular formula	C26H27FN10
Molecular weight	498.6
InChIKey	DWYRIWUZIJHQKQ-SANMLTNESA-N

SMILES: C[C@](C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N

IUPAC name: (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine

Also known as: 70C366, Avapritinib, Ayvakit, Ayvakyt, BLU-285, C-366, X-720776, X720776, AVAPRITINIB, Avarpritinib, US10807985, Compound 44

Patent coverage: 529 distinct patent families (1,306 SureChEMBL compound mentions), from 1 matched compound structure(s). 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	7.14	0.5%	P10721

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Mast/stem cell growth factor receptor Kit, Platelet-derived growth factor receptor alpha, Broad substrate specificity ATP-binding cassette transporter ABCG2.

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
KIT	9.7	IC50	0.2	nM	CHEMBL_ACT_29279065
PDGFRA	9.62	IC50	0.24	nM	CHEMBL_ACT_26186122
KIT	9.62	IC50	0.24	nM	CHEMBL_ACT_26186123
PDGFRA	9.62	IC50	0.24	nM	CHEMBL_ACT_29055503
KIT	9.57	IC50	0.27	nM	CHEMBL_ACT_26186120
KIT	9.57	IC50	0.27	nM	CHEMBL_ACT_29055502
ABCG2	8.82	IC50	1.5	nM	CHEMBL_ACT_24963508
PDGFRA	8.48	IC50	3.3	nM	CHEMBL_ACT_29168405
KIT	8.24	IC50	5.8	nM	CHEMBL_ACT_29279027
PDGFRA	7.72	IC50	19.1	nM	CHEMBL_ACT_29168393
KIT	5.82	IC50	1518	nM	CHEMBL_ACT_29279095
PDGFRA	5.39	IC50	4039	nM	CHEMBL_ACT_29279197

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
Sorafenib-resistant KIT mutants	1	KIT
Drug resistance of KIT mutants	1	KIT
Signaling by KIT in disease	1	KIT
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	KIT
Signaling by extracellular domain mutants of KIT	1	KIT
MITF-M-regulated melanocyte development	1	KIT
Transcriptional and post-translational regulation of MITF-M expression and activity	1	KIT
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	KIT
Developmental Lineage of Mammary Gland Alveolar Cells	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

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
neoplasm	4	MONDO:0005070	EFO:0000616
gastrointestinal stromal tumor	4	MONDO:0011719	MONDO:0011719

3 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
mast cell leukemia	2	MONDO:0020334	EFO:0007359
acute myeloid leukemia	2	MONDO:0018874	EFO:0000222
central nervous system cancer	1	MONDO:0002714	EFO:0000326

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

Clinical trials

Total trials: 22.

Phase distribution

Phase	Trials
PHASE2	9
Not specified	5
PHASE1	4
PHASE4	2
PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06748001	PHASE4	RECRUITING	Avapritinib Rollover Study
NCT04825574	PHASE4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT03465722	PHASE3	COMPLETED	(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
NCT03731260	PHASE2	ACTIVE_NOT_RECRUITING	(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis
NCT04116541	PHASE2	RECRUITING	A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors.
NCT04771520	PHASE2	RECRUITING	Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors
NCT06221683	PHASE2	RECRUITING	Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML
NCT06316960	PHASE2	RECRUITING	Safety and Efficacy of Avapritinib in Relapsed or Refractory Pediatric CBF-AML With KIT Mutation
NCT06765915	PHASE2	NOT_YET_RECRUITING	Avapritinib Maintenance for AML With KIT Mutations
NCT06783790	PHASE2	RECRUITING	Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed AML After Allo-HSCT
NCT03580655	PHASE2	COMPLETED	(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis
NCT04773782	PHASE1/PHASE2	COMPLETED	A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling
NCT05821738	PHASE2	UNKNOWN	Avapritinib in CBF-AML With KIT Mutations
NCT06327685	PHASE1	RECRUITING	Avapritinib With Decitabine in Patients With SM-AHN
NCT02508532	PHASE1	COMPLETED	(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
NCT02561988	PHASE1	COMPLETED	(EXPLORER) Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies
NCT04908176	PHASE1	COMPLETED	A Drug-drug Interaction Study of Avapritinib and Midazolam
NCT07131059	Not specified	RECRUITING	MRD-positive AML Clinical Study
NCT07255638	Not specified	RECRUITING	A Non-Interventional Study in Participants With Indolent Systemic Mastocytosis (ISM) in Germany
NCT03862885	Not specified	APPROVED_FOR_MARKETING	Early Access Program (EAP) for Avapritinib in Patients With Locally Advanced Unresectable or Metastatic GIST
NCT04714086	Not specified	NO_LONGER_AVAILABLE	Expanded Access Program for Avapritinib
NCT05381753	Not specified	COMPLETED	Safety and Efficacy of Avapritinib in Chinese Patients With Gastrointestinal Stromal Tumor (GIST) in the Real World

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
KIT D816V	Systemic Mastocytosis	Sensitivity/Response	Avapritinib	CIViC A	EID11274
PDGFRA Exon 18 Mutation	Gastrointestinal Stromal Tumor	Sensitivity/Response	Avapritinib	CIViC A	EID7809
PDGFRA D842V	Gastrointestinal Stromal Tumor	Sensitivity/Response	Avapritinib	CIViC B	EID7479

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.

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

Molecule	Source	Status	Shared targets
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
BEZUCLASTINIB	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
DEFOSBARASERTIB	ChEMBL	Phase 2	KIT
DENFIVONTINIB	ChEMBL	Phase 2	KIT
DORAMAPIMOD	ChEMBL	Phase 2	KIT
EDICOTINIB	ChEMBL	Phase 2	KIT
ELLIPTINIUM	ChEMBL	Phase 2	KIT
ENMD-2076	ChEMBL	Phase 2	KIT
ENRUPATINIB	ChEMBL	Phase 2	KIT
FORETINIB	ChEMBL	Phase 2	KIT
ILORASERTIB	ChEMBL	Phase 2	KIT
LABUXTINIB	ChEMBL	Phase 2	KIT
MILCICLIB	ChEMBL	Phase 2	KIT
R-406	ChEMBL	Phase 2	KIT
RAF-265	ChEMBL	Phase 2	KIT
REBASTINIB	ChEMBL	Phase 2	KIT
RISVODETINIB	ChEMBL	Phase 2	KIT
SOTULETINIB	ChEMBL	Phase 2	KIT
SU-014813	ChEMBL	Phase 2	KIT
TANDUTINIB	ChEMBL	Phase 2	KIT
TELATINIB	ChEMBL	Phase 2	KIT
TOZASERTIB	ChEMBL	Phase 2	KIT
Afatinib	PubChem	Approved	KIT
Idelalisib	PubChem	Approved	KIT
Selumetinib	PubChem	Approved	KIT