Fruquintinib

Summary

Fruquintinib (CHEMBL4303214) is an approved small-molecule EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor (ATC L01EK04) targeting FLT1, KDR, and FLT4; indicated across 21 conditions including neoplasm and colorectal adenocarcinoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EK04
• Targets: 3 (FLT1, KDR, FLT4)
• Indications: 21 conditions
• Clinical trials: 121
• Chemistry: 393.4 Da · C21H19N3O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4303214
Name	Fruquintinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	44480399
ChEBI	CHEBI:229221
ATC	L01EK04
Molecular formula	C21H19N3O5
Molecular weight	393.4
InChIKey	BALLNEJQLSTPIO-UHFFFAOYSA-N

SMILES: CC1=C(C2=C(O1)C=C(C=C2)OC3=NC=NC4=CC(=C(C=C43)OC)OC)C(=O)NC

IUPAC name: 6-(6,7-dimethoxyquinazolin-4-yl)oxy-N,2-dimethyl-1-benzofuran-3-carboxamide

ChEBI definition: A member of the class of quinazolines that is quinazoline substituted by [2-methyl-3-(methylcarbamoyl)-1-benzofuran-6-yl]oxy, methoxy, and methoxy groups at positions 4, 6, and 7, respectively. It is a highly potent and selective inhibitor of VEGFR 1, 2 and 3 (IC50 = 33, 0.35, and 35 nM) used for the treatment of metastatic colorectal cancer.

Pharmacological roles (ChEBI): EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, antineoplastic agent, vascular endothelial growth factor receptor antagonist.

Also known as: Fruquintinib, Fruzaqla, Hmpl-013, HMPL-013, HMPL013, FRUQUINTINIB, fruquintinib

Patent coverage: 292 distinct patent families (732 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 657 (90%) 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
FLT1	fms related receptor tyrosine kinase 1	Inhibition	7.48	0.1%	P17948
KDR	kinase insert domain receptor	Inhibition	7.46	1.1%	P35968
FLT4	fms related receptor tyrosine kinase 4	Inhibition	9.3	0.2%	P35916

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Vascular endothelial growth factor receptor 1, Vascular endothelial growth factor receptor 3, Vascular endothelial growth factor receptor 2.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
KDR	9.46	IC50	0.35	nM	CHEMBL_ACT_25871814
KDR	9.46	IC50	0.35	nM	CHEMBL_ACT_25905428
FLT1	7.48	IC50	33	nM	CHEMBL_ACT_25871813
FLT1	7.48	IC50	33	nM	CHEMBL_ACT_25905427
FLT4	7.46	IC50	35	nM	CHEMBL_ACT_25871815
FLT4	7.46	IC50	35	nM	CHEMBL_ACT_25905429
FLT1	7.46	IC50	35	nM	CHEMBL_ACT_26150877
FLT4	7.46	IC50	35	nM	CHEMBL_ACT_26150880
KDR	7.46	IC50	35	nM	CHEMBL_ACT_26150885

Target pathways

Aggregated over 3 target gene(s): FLT1, KDR, FLT4.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
VEGF binds to VEGFR leading to receptor dimerization	3	FLT1, FLT4, KDR
Neuropilin interactions with VEGF and VEGFR	2	FLT1, KDR
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	2	FLT4, KDR
Integrin cell surface interactions	1	KDR
VEGFA-VEGFR2 Pathway	1	KDR
VEGFR2 mediated cell proliferation	1	KDR
NOTCH4 Intracellular Domain Regulates Transcription	1	FLT4
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	KDR

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
peptidyl-tyrosine phosphorylation	3
positive regulation of cell migration	3
cellular response to vascular endothelial growth factor stimulus	3
positive regulation of MAPK cascade	3
protein autophosphorylation	3
vascular endothelial growth factor receptor signaling pathway	3
angiogenesis	3
protein phosphorylation	3
vascular endothelial growth factor signaling pathway	3
sprouting angiogenesis	2
cell differentiation	2
positive regulation of angiogenesis	2

Indications & clinical

Indications

21 indications (5 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
colorectal adenocarcinoma	4	MONDO:0005008	EFO:0000365
colorectal neoplasm	4	MONDO:0005335	EFO:0004142
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
gastric neoplasm	3	MONDO:0021085	MONDO:0001056
rectal cancer	2	MONDO:0006519	EFO:1000657
lung neoplasm	2	MONDO:0021117	MONDO:0008903
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
soft tissue sarcoma	2	MONDO:0018078	EFO:1001968
colonic neoplasm	2	MONDO:0005401	MONDO:0021063
renal cell carcinoma	2	MONDO:0005086	EFO:0000681
esophageal squamous cell carcinoma	2	MONDO:0005580	EFO:0005922
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
breast neoplasm	1	MONDO:0021100	MONDO:0007254
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086
endometrium neoplasm	1	MONDO:0021251	MONDO:0011962
adenocarcinoma	1	MONDO:0004970	MONDO:0003219

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

Clinical trials

Total trials: 121.

Phase distribution

Phase	Trials
PHASE2	69
Not specified	14
PHASE3	12
PHASE1	11
PHASE1/PHASE2	8
PHASE4	3
PHASE2/PHASE3	3
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06118762	PHASE4	RECRUITING	Clinical Study of Fruquintinib Combined With Raltitrexed in the Treatment of Metastatic Colorectal Cancer
NCT06562543	PHASE4	RECRUITING	A Trial to Evaluate the Safety and Activity of Fruquintinib in Minority Populations With Advanced, Previously Treated Colorectal Cancer
NCT07446465	PHASE4	NOT_YET_RECRUITING	FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer
NCT04164199	PHASE3	ACTIVE_NOT_RECRUITING	Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies
NCT05522231	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Fruquintinib in Combination With Sintilimab in Advanced Renal Cell Carcinoma (FRUSICA-2)
NCT05914610	PHASE3	NOT_YET_RECRUITING	Envollizumab Combined With Fruquintinib and SOX Versus SOX for Conversion Therapy in Advanced Gastric Cancer
NCT06199973	PHASE3	ACTIVE_NOT_RECRUITING	Injection of SHR-A1811 Versus Physician Choiced Treatment in Patients With Advanced Colorectal Cancer Who Had Failed to Respond to Oxaliplatin, 5-fu, and Irinotecan
NCT06441565	PHASE2/PHASE3	RECRUITING	Fruquintinib With or Without HAI-FOLFOX for Refractory Colorectal Cancer
NCT06443671	PHASE2/PHASE3	NOT_YET_RECRUITING	Neoadjuvant Fruquintinib Plus Tislelizumab Combined With mCapeOX Versus CapeOX for Mid-high pMMR/MSS Locally Advanced Rectal Cancer
NCT06497985	PHASE3	RECRUITING	A Study of Tucidinostat in Combination With Sintilimab and Bevacizumab in MSS/pMMR Colorectal Cancer Patients
NCT06584032	PHASE3	RECRUITING	Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer
NCT07270991	PHASE3	RECRUITING	Trifluridine/Tipiracil + Fruquintinib Versus Trifluridine/Tipiracil Alone for Metastatic Oeso-gastric Adenocarcinoma
NCT07362836	PHASE3	NOT_YET_RECRUITING	Fruquintinib Versus Bevacizumab Plus Chemotherapy in Second-Line RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS)
NCT07483684	PHASE3	NOT_YET_RECRUITING	A Clinical Study to Evaluate Injection TQB2102 for the Treatment of Patients With HER2 IHC3+ Advanced Colorectal Cancer Who Progressed After Treatment With Oxaliplatin, Irinotecan and Fluoropyrimidine-Based Drugs
NCT02314819	PHASE3	COMPLETED	A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients （FRESCO)
NCT02691299	PHASE3	COMPLETED	A Phase III Clinical Trial of Fruquintinib in Patients With Advanced Non-small Cell Lung Cancer
NCT03223376	PHASE3	COMPLETED	A Phase III Study of Fruquintinib in Combination With Paclitaxel in Second Line Gastric Cancer(FRUTIGA)
NCT04322539	PHASE3	COMPLETED	A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer
NCT05177068	PHASE2	ACTIVE_NOT_RECRUITING	Conversion Therapy of Fruquintinib in Combination With Sintilimab and SOX in Unresectable Gastric Cancer
NCT05565417	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of the Monoclonal Antibody IMT-009 in Patients With Advanced Solid Tumors or Lymphomas
NCT05571644	PHASE2	RECRUITING	Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer
NCT05747716	PHASE2	NOT_YET_RECRUITING	SBRT Combined With Fruquintinib Plus PD-1/CTLA-4 Antibody for Third-line Treatment in mCRC
NCT05771181	PHASE2	RECRUITING	Vitamin E Combined With Fruquintinib and Tislelizumab in Microsatellite Stabilized Metastatic Colorectal Cancer Patients
NCT05867420	PHASE1/PHASE2	RECRUITING	A Study of ASKG915 in Patients With Selected Advanced Solid Tumors.
NCT05954429	PHASE2	RECRUITING	A Study to Explore the Third-line Treatment of Fruquintinib Combined With Serplulimab in Advanced Non-liver-limited Metastatic Colorectal Cancer: a Single-center, Phase 2 Study
NCT06018714	PHASE2	RECRUITING	Efficacy of Modified Fruquintinib in Colorectal Cancer Liver Metastases: A Phase II Study
NCT06094868	PHASE2	NOT_YET_RECRUITING	Clinical Study of Fruquintinib Combined With Sintilimab and XELOX Regimen in the Treatment of Advanced Cancer
NCT06168786	PHASE2	RECRUITING	Cadonilimab Combined With Fruquintinib and SBRT as Athird-line and Posterior Line Treatment in Patients With MSS CRC
NCT06218888	PHASE2	NOT_YET_RECRUITING	A Phase II Clinical Study of the Efficacy and Safety of Tislelizumab Combined With Fruquintinib and Chidamide in the Treatment of Unresectable or Advanced Microsatellite Stabilized (MSS/pMMR) Colorectal Cancer With Liver Metastases
NCT06234007	PHASE2	RECRUITING	Short-course Radiotherapy Followed by Fruquintinib Plus Adebrelimab and CAPOX in the Full Course Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Multicenter, Single-arm, Open-label Study
NCT06427005	PHASE2	RECRUITING	Fruquintinib Plus S-1 and Raltitrexed (RSF) for MCRC
NCT06446154	PHASE2	RECRUITING	Fruquintinib After ICIs Treatment in Unresectable Hepatocellular Carcinoma
NCT06484153	PHASE1/PHASE2	NOT_YET_RECRUITING	Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma
NCT06543836	PHASE2	RECRUITING	ctDNA-guided Treatment of TKI Plus PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer
NCT06646588	PHASE2	RECRUITING	Fruquintinib in Combination With Tislelizumab Followed by Radiotherapy in Esophageal Squamous Cell Carcinoma
NCT06685276	PHASE2	RECRUITING	Safety and Efficacy of Fruquintinib Plus Chidamide and Sintilimab in the Third and Later Line Treatment of MSS/pMMR Metastatic Colorectal Cancer
NCT06746545	PHASE2	NOT_YET_RECRUITING	A Prospective, Open-label, Single-arm Phase II Clinical Study of Fruquintinib Combined With S-1 for the Treatment of Metastatic Colorectal Cancer.
NCT06774222	PHASE2	RECRUITING	A Study of Fruquintinib Plus Chemotherapy for Postoperative Treatment of HER2-Negative Gastric Cancer With Poor TRG
NCT06791083	PHASE2	RECRUITING	Clinical Study of Envafolimab Combined With Fruquintinib and Chemotherapy for Neoadjuvant Treatment of Gastric Cancer
NCT06856837	PHASE2	RECRUITING	- IKF/AIO-QUINTIS - Evaluating Fruquintinib in Combination With Tislelizumab in Microsatellite Stable / Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Cancer Without Active Liver Metastases

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.

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

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR
Gefitinib	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, FLT4, KDR
AXITINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
ENTRECTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
ERLOTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
FEDRATINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
INFIGRATINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
LENVATINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
NINTEDANIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
NINTEDANIB ESYLATE	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
QUIZARTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
SORAFENIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
SUNITINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
TIVOZANIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
VANDETANIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4, KDR
BRIVANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
CEDIRANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
CEP-1347	ChEMBL	Phase 3	FLT1, FLT4, KDR
DOVITINIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
LESTAURTINIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
LINIFANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
MOTESANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
SEMAXANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
SURUFATINIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
VATALANIB	ChEMBL	Phase 3	FLT1, FLT4, KDR
AT-9283	ChEMBL	Phase 2	FLT1, FLT4, KDR
BFH-772	ChEMBL	Phase 2	FLT1, FLT4, KDR
CENISERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
DEFOSBARASERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
DORAMAPIMOD	ChEMBL	Phase 2	FLT1, FLT4, KDR
FORETINIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
ILORASERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
LUCITANIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
MK-2461	ChEMBL	Phase 2	FLT1, FLT4, KDR
OSI-632	ChEMBL	Phase 2	FLT1, FLT4, KDR
R-406	ChEMBL	Phase 2	FLT1, FLT4, KDR
RAF-265	ChEMBL	Phase 2	FLT1, FLT4, KDR
REBASTINIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
SU-014813	ChEMBL	Phase 2	FLT1, FLT4, KDR
TANDUTINIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
TOZASERTIB	ChEMBL	Phase 2	FLT1, FLT4, KDR
Afatinib	PubChem	Approved	FLT1, FLT4, KDR
Selumetinib	PubChem	Approved	FLT1, FLT4, KDR
BRIGATINIB	ChEMBL	Phase 4 (approved)	FLT4, KDR
DASATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR
FILGOTINIB	ChEMBL	Phase 4 (approved)	FLT1, FLT4
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR
PONATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR
ALISERTIB	ChEMBL	Phase 3	FLT1, KDR
CANERTINIB	ChEMBL	Phase 3	FLT1, KDR
DEFACTINIB	ChEMBL	Phase 3	FLT1, KDR
ORANTINIB	ChEMBL	Phase 3	FLT1, KDR
AEE-788	ChEMBL	Phase 2	FLT1, KDR
CEP-11981	ChEMBL	Phase 2	FLT1, KDR
CEP-32496	ChEMBL	Phase 2	FLT1, KDR
DANUSERTIB	ChEMBL	Phase 2	FLT4, KDR