Ripretinib

Summary

Ripretinib (CHEMBL4216467) is an approved small molecule (ATC L01EX19) targeting KIT; indicated across 2 conditions including neoplasm and gastrointestinal stromal tumor; with CIViC clinical evidence for 2 variant-indication associations (e.g. KIT Mutation in gastrointestinal stromal tumor).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EX19
• Targets: 1 (KIT)
• Indications: 2 conditions
• Clinical trials: 13
• Precision-oncology evidence (CIViC): 2 variant–indication associations
• Chemistry: 510.4 Da · C24H21BrFN5O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4216467
Name	Ripretinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	71584930
ATC	L01EX19
Molecular formula	C24H21BrFN5O2
Molecular weight	510.4
InChIKey	CEFJVGZHQAGLHS-UHFFFAOYSA-N

SMILES: CCN1C2=CC(=NC=C2C=C(C1=O)C3=CC(=C(C=C3Br)F)NC(=O)NC4=CC=CC=C4)NC

IUPAC name: 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea

Also known as: Dcc-2618, DCC-2618, Qinlock, Ripretinib, RIPRETINIB

Patent coverage: 415 distinct patent families (1,068 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 967 (91%) 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		0.5%	P10721

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Mast/stem cell growth factor receptor Kit, Platelet-derived growth factor receptor alpha.

Bioactivity

ChEMBL activities: 11 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDGFRA	9.22	IC50	0.6	nM	CHEMBL_ACT_29279128
PDGFRA	9.15	IC50	0.7	nM	CHEMBL_ACT_29279162
KIT	8.77	IC50	1.7	nM	CHEMBL_ACT_29279026
KIT	8.74	IC50	1.8	nM	CHEMBL_ACT_29279064
KIT	8.04	IC50	9.2	nM	CHEMBL_ACT_25016217
KIT	7.89	IC50	13	nM	CHEMBL_ACT_25016214
KIT	7.82	IC50	15	nM	CHEMBL_ACT_25688585
KIT	7.51	IC50	31	nM	CHEMBL_ACT_25688581
KIT	6.73	IC50	185	nM	CHEMBL_ACT_25688589
PDGFRA	6.43	IC50	375	nM	CHEMBL_ACT_29279196
KIT	6.19	IC50	642	nM	CHEMBL_ACT_29279094

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

2 indications (2 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
gastrointestinal stromal tumor	4	MONDO:0011719	MONDO:0011719

Clinical trials

Total trials: 13.

Phase distribution

Phase	Trials
Not specified	4
PHASE3	3
PHASE2	2
PHASE1/PHASE2	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03673501	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
NCT05734105	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
NCT03353753	PHASE3	COMPLETED	Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies
NCT05957367	PHASE1/PHASE2	RECRUITING	A Study of Inlexisertib (DCC-3116) in Combination With Anticancer Therapies in Participants With Advanced Malignancies
NCT04282980	PHASE2	COMPLETED	A Study of DCC-2618 (Ripretinib) In Patients With With Advanced Gastrointestinal Stromal Tumors (GIST)
NCT04633122	PHASE2	COMPLETED	A Study to Assess DCC-2618 and Sunitinib in Patients With Advanced GIST After Treatment With Imatinib
NCT05080621	PHASE1/PHASE2	WITHDRAWN	Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)
NCT02571036	PHASE1	COMPLETED	A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies
NCT04530981	PHASE1	COMPLETED	A Drug-Drug Interaction Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate in Patients with Advanced GIST
NCT04148092	Not specified	APPROVED_FOR_MARKETING	Expanded Access Program of Ripretinib (DCC-2618) for the Treatment of Patients With Advanced GIST
NCT05132738	Not specified	UNKNOWN	Ripretinib Used for Resectable Metastatic GIST After Failure of Imatinib Therapy
NCT05697107	Not specified	UNKNOWN	Ripretinib in Chinese Patients With Advanced GIST: a Real World Study
NCT06619275	Not specified	COMPLETED	Ripretinib (QINLOCK®) According to Current SmPC

Clinical evidence (CIViC)

Variant × indication × effect (2 predictive associations from 2 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
KIT Mutation	Gastrointestinal Stromal Tumor	Sensitivity/Response	Ripretinib	CIViC A	EID11284
PDGFRA Mutation	Gastrointestinal Stromal Tumor	Sensitivity/Response	Ripretinib	CIViC A	EID11333

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 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
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