Orantinib

Summary

Orantinib (CHEMBL274654) is a phase-3 clinical-stage small molecule targeting EGFR, PDGFRB, and FGFR1; indicated across 10 conditions including hepatocellular carcinoma and neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (EGFR, PDGFRB, FGFR1…)
• Indications: 10 conditions
• Clinical trials: 4
• Chemistry: 310.3 Da · C18H18N2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL274654
Name	Orantinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5329099
Molecular formula	C18H18N2O3
Molecular weight	310.3
InChIKey	NHFDRBXTEDBWCZ-ZROIWOOFSA-N

SMILES: CC1=C(NC(=C1CCC(=O)O)C)/C=C\2/C3=CC=CC=C3NC2=O

IUPAC name: 3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid

Also known as: NSC-702827, Orantinib, SU-006668, Su-6668, SU-6668, Su006668, TSU-68, SU6668, SID527809, ORANTINIB, TSU-68 (SU6668, Orantinib), orantinib

Patent coverage: 1,415 distinct patent families (3,596 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 3,376 (94%) 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
EGFR	epidermal growth factor receptor	Inhibition	4	17.5%	P00533
PDGFRB	platelet derived growth factor receptor beta	Inhibition	7.3	2.3%	P09619
FGFR1	fibroblast growth factor receptor 1	Inhibition	5.74	11.5%	P11362
KDR	kinase insert domain receptor	Inhibition	6.17	1.1%	P35968

Broader ChEMBL bioactivity targets: 34 (assay-derived). Sample: Vascular endothelial growth factor receptor 1, Platelet-derived growth factor receptor beta, Receptor-type tyrosine-protein kinase FLT3, Proto-oncogene tyrosine-protein kinase receptor Ret, Platelet-derived growth factor receptor, Aurora kinase B, Ribosomal protein S6 kinase alpha-1, Mitogen-activated protein kinase kinase kinase 11, Vascular endothelial growth factor receptor 2, Tyrosine-protein kinase ZAP-70.

Bioactivity

ChEMBL activities: 54 potent at pChembl ≥ 5 of 60 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
FGFR1	9.52	Kd	0.3	nM	CHEMBL_ACT_17903353
FLT3	9.1	Kd	0.8	nM	CHEMBL_ACT_17903687
TNIK	7.92	Kd	12	nM	CHEMBL_ACT_17945389
BMPR2	7.72	Kd	19	nM	CHEMBL_ACT_17885648
FLT1	7.55	IC50	28	nM	CHEMBL_ACT_11019133
AURKB	7.46	IC50	35	nM	CHEMBL_ACT_2897261
AURKB	7.33	IC50	47	nM	CHEMBL_ACT_18761192
AURKB	7.33	IC50	47	nM	CHEMBL_ACT_25855088
PDGFRB	7.3	IC50	50	nM	CHEMBL_ACT_2488848
PDGFRB	7.22	IC50	60	nM	CHEMBL_ACT_29065549
PDGFRB	7.22	IC50	60	nM	CHEMBL_ACT_514083
PDGFRB	7.22	IC50	60	nM	CHEMBL_ACT_714961
PDGFRB	7	IC50	100	nM	CHEMBL_ACT_3299671
KDR	6.87	IC50	135	nM	CHEMBL_ACT_11020089
AURKC	6.68	IC50	210	nM	CHEMBL_ACT_2897265
BMP2K	6.52	Kd	303	nM	CHEMBL_ACT_17884877
P05622	6.52	IC50	300	nM	CHEMBL_ACT_714970
RET	6.5	Kd	316	nM	CHEMBL_ACT_17935185
KDR	6.39	IC50	410	nM	CHEMBL_ACT_514085
KDR	6.17	IC50	680	nM	CHEMBL_ACT_2488847
PDGFRB	6.13	Kd	744	nM	CHEMBL_ACT_17924575
AURKB	6.03	Kd	933	nM	CHEMBL_ACT_17884378
P05622	6	IC50	1000	nM	CHEMBL_ACT_714965
AAK1	5.93	Kd	1174	nM	CHEMBL_ACT_17878174
Q6ZSR9	5.93	Kd	1183	nM	CHEMBL_ACT_17933779
NAT10	5.91	Kd	1240	nM	CHEMBL_ACT_17920605
RPS6KA4	5.86	Kd	1388	nM	CHEMBL_ACT_17936855
IKBKE	5.84	Kd	1430	nM	CHEMBL_ACT_17907330
ULK3	5.84	Kd	1455	nM	CHEMBL_ACT_17947577
STK4	5.8	Kd	1567	nM	CHEMBL_ACT_17942225

Target pathways

Aggregated over 4 target gene(s): EGFR, PDGFRB, FGFR1, KDR.

Top Reactome pathways

63 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	3	EGFR, FGFR1, PDGFRB
Constitutive Signaling by Aberrant PI3K in Cancer	3	EGFR, FGFR1, PDGFRB
RAF/MAP kinase cascade	3	EGFR, FGFR1, PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	3	EGFR, FGFR1, PDGFRB
Signal transduction by L1	2	EGFR, FGFR1
PI3K Cascade	1	FGFR1
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
Signaling by FGFR1 amplification mutants	1	FGFR1
Signaling by activated point mutants of FGFR1	1	FGFR1
Downstream signal transduction	1	PDGFRB
Signaling by PDGF	1	PDGFRB
FGFR1b ligand binding and activation	1	FGFR1
FGFR1c ligand binding and activation	1	FGFR1
FGFR1c and Klotho ligand binding and activation	1	FGFR1
Neuropilin interactions with VEGF and VEGFR	1	KDR
VEGF binds to VEGFR leading to receptor dimerization	1	KDR
GRB2 events in ERBB2 signaling	1	EGFR
PI3K events in ERBB2 signaling	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
Integrin cell surface interactions	1	KDR
EGFR Transactivation by Gastrin	1	EGFR

Dominant GO biological processes

GO term	Targets
positive regulation of cell population proliferation	4
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	4
protein phosphorylation	4
positive regulation of cell migration	3
positive regulation of MAPK cascade	3
positive regulation of ERK1 and ERK2 cascade	3
cell surface receptor protein tyrosine kinase signaling pathway	3
angiogenesis	3
peptidyl-tyrosine phosphorylation	3
protein autophosphorylation	3
cell migration	3
positive regulation of protein phosphorylation	2
signal transduction	2
salivary gland morphogenesis	2
gene expression	2

Indications & clinical

Indications

10 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
hepatocellular carcinoma	3	MONDO:0007256	EFO:0000182
neoplasm	1	MONDO:0005070	EFO:0000616
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618
gastric neoplasm	1	MONDO:0021085	MONDO:0001056
kidney cancer	1	MONDO:0002367	MONDO:0002367
breast neoplasm	1	MONDO:0021100	MONDO:0007254
lung neoplasm	1	MONDO:0021117	MONDO:0008903
colorectal neoplasm	1	MONDO:0005335	MONDO:0005575

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

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE1	2
PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01465464	PHASE3	TERMINATED	Orantinib In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma
NCT00784290	PHASE1/PHASE2	COMPLETED	Phase I/II Study of TSU-68 for Advanced Hepatocellular Carcinoma
NCT00024063	PHASE1	UNKNOWN	SU006668 in Treating Patients With Advanced Solid Tumors
NCT00024206	PHASE1	COMPLETED	SU6668 in Treating Patients With Advanced Solid 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.

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

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
VANDETANIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR, PDGFRB
BRIVANIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR, PDGFRB
CEDIRANIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR, PDGFRB
DOVITINIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR, PDGFRB
LESTAURTINIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR, PDGFRB
LINIFANIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR, PDGFRB
MOTESANIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR, PDGFRB
CENISERTIB	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
DORAMAPIMOD	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
FORETINIB	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
ILORASERTIB	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
OSI-632	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
R-406	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
SU-014813	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
TANDUTINIB	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
TOZASERTIB	ChEMBL	Phase 2	EGFR, FGFR1, KDR, PDGFRB
Binimetinib	PubChem	Approved	EGFR, FGFR1, KDR, PDGFRB
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, FGFR1, PDGFRB
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, FGFR1, KDR
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	FGFR1, KDR, PDGFRB
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR, PDGFRB
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR, KDR, PDGFRB
LENVATINIB	ChEMBL	Phase 4 (approved)	FGFR1, KDR, PDGFRB
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR, FGFR1, KDR
NINTEDANIB	ChEMBL	Phase 4 (approved)	FGFR1, KDR, PDGFRB
NINTEDANIB ESYLATE	ChEMBL	Phase 4 (approved)	FGFR1, KDR, PDGFRB
TIVOZANIB	ChEMBL	Phase 4 (approved)	FGFR1, KDR, PDGFRB
ALISERTIB	ChEMBL	Phase 3	EGFR, FGFR1, KDR
BARASERTIB	ChEMBL	Phase 3	EGFR, KDR, PDGFRB
CANERTINIB	ChEMBL	Phase 3	EGFR, KDR, PDGFRB
RUBOXISTAURIN	ChEMBL	Phase 3	EGFR, FGFR1, PDGFRB
SARACATINIB	ChEMBL	Phase 3	EGFR, KDR, PDGFRB
SEMAXANIB	ChEMBL	Phase 3	FGFR1, KDR, PDGFRB
VATALANIB	ChEMBL	Phase 3	EGFR, KDR, PDGFRB
AEE-788	ChEMBL	Phase 2	EGFR, KDR, PDGFRB
CEP-32496	ChEMBL	Phase 2	EGFR, KDR, PDGFRB
DEFOSBARASERTIB	ChEMBL	Phase 2	EGFR, KDR, PDGFRB
ELLAGIC ACID	ChEMBL	Phase 2	EGFR, KDR, PDGFRB
LUCITANIB	ChEMBL	Phase 2	FGFR1, KDR, PDGFRB
MILCICLIB	ChEMBL	Phase 2	EGFR, FGFR1, PDGFRB
MK-2461	ChEMBL	Phase 2	FGFR1, KDR, PDGFRB
RAF-265	ChEMBL	Phase 2	FGFR1, KDR, PDGFRB
SOTRASTAURIN	ChEMBL	Phase 2	EGFR, KDR, PDGFRB
TOCERANIB	ChEMBL	Phase 2	FGFR1, KDR, PDGFRB
VERUBULIN	ChEMBL	Phase 2	EGFR, KDR, PDGFRB
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	EGFR, KDR
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR, KDR