Rivoceranib

Summary

Rivoceranib (CHEMBL3186534) is a phase-3 clinical-stage small molecule targeting KIT, KDR, and CSK; indicated across 66 conditions including hepatocellular carcinoma and gastric adenocarcinoma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (KIT, KDR, CSK…)
• Indications: 66 conditions
• Clinical trials: 444
• Chemistry: 397.5 Da · C24H23N5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3186534
Name	Rivoceranib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11315474
Molecular formula	C24H23N5O
Molecular weight	397.5
InChIKey	WPEWQEMJFLWMLV-UHFFFAOYSA-N

SMILES: C1CCC(C1)(C#N)C2=CC=C(C=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4

IUPAC name: N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide

Also known as: Apatinib, Apatinib free base, Rivoceranib, YN968D1, YN968D1 FREE BASE, SID124955476, RIVOCERANIB, APATINIB, Apatinib mesylate

Parent form; salt/anhydrous children: CHEMBL3545414

Patent coverage: 1,122 distinct patent families (2,337 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 2,291 (98%) 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	6.37	0.5%	P10721
KDR	kinase insert domain receptor	Inhibition	9	1.1%	P35968
CSK	C-terminal Src kinase	Inhibition	6.28	5.5%	P41240
RET	ret proto-oncogene	Inhibition	7.89	0.4%	P07949

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Receptor-interacting serine/threonine-protein kinase 3, Proto-oncogene tyrosine-protein kinase receptor Ret, Mitogen-activated protein kinase kinase kinase 20.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 3 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
RET	6.96	Kd	111	nM	CHEMBL_ACT_17935085
RIPK3	5.62	Kd	2373	nM	CHEMBL_ACT_17935534
MAP3K20	5.32	Kd	4760	nM	CHEMBL_ACT_17948485

Target pathways

Aggregated over 4 target gene(s): KIT, KDR, CSK, RET.

Top Reactome pathways

63 total, by targets touching each:

Pathway	Targets	Genes
RAF/MAP kinase cascade	2	KIT, RET
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
GAB1 signalosome	1	CSK
Neuropilin interactions with VEGF and VEGFR	1	KDR
VEGF binds to VEGFR leading to receptor dimerization	1	KDR
Negative regulation of the PI3K/AKT network	1	KIT
Phosphorylation of CD3 and TCR zeta chains	1	CSK
Generic Transcription Pathway	1	KIT
Integrin cell surface interactions	1	KDR
PI3K/AKT Signaling in Cancer	1	KIT
Constitutive Signaling by Aberrant PI3K in Cancer	1	KIT
Integrin signaling	1	CSK
Co-inhibition by PD-1	1	CSK
VEGFA-VEGFR2 Pathway	1	KDR
VEGFR2 mediated cell proliferation	1	KDR
Diseases of signal transduction by growth factor receptors and second messengers	1	KIT
MAP2K and MAPK activation	1	CSK
MAPK family signaling cascades	1	KIT
MAPK1/MAPK3 signaling	1	KIT
Signaling by moderate kinase activity BRAF mutants	1	CSK
Signaling by high-kinase activity BRAF mutants	1	CSK
Signaling by BRAF and RAF1 fusions	1	CSK
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	CSK
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	KIT
RNA Polymerase II Transcription	1	KIT

Dominant GO biological processes

GO term	Targets
protein phosphorylation	4
positive regulation of cell migration	3
positive regulation of MAPK cascade	3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3
cell surface receptor protein tyrosine kinase signaling pathway	3
ovarian follicle development	2
signal transduction	2
positive regulation of cell population proliferation	2
regulation of cell shape	2
cell migration	2
hemopoiesis	2
embryonic hemopoiesis	2
intracellular signal transduction	2
protein autophosphorylation	2
epithelial cell proliferation	2

Indications & clinical

Indications

66 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
gastric adenocarcinoma	3	MONDO:0005036	EFO:0000503
gastric carcinoma	3	MONDO:0004950	EFO:0000178
colorectal adenocarcinoma	3	MONDO:0005008	EFO:0000365
small cell lung carcinoma	3	MONDO:0008433	EFO:0000702
melanoma	3	MONDO:0005105	EFO:0000756
thyroid gland carcinoma	3	MONDO:0015075	EFO:0002892
carcinoma of esophagus	3	MONDO:0019086	EFO:0002916
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
breast neoplasm	3	MONDO:0021100	EFO:0003869
ovarian neoplasm	3	MONDO:0021068	EFO:0003893
gastric neoplasm	3	MONDO:0021085	EFO:0003897
colorectal neoplasm	3	MONDO:0005335	EFO:0004142
esophageal squamous cell carcinoma	3	MONDO:0005580	EFO:0005922
adenocarcinoma	3	MONDO:0004970	MONDO:0003219
ovarian cancer	3	MONDO:0008170	MONDO:0008170
nasopharyngeal carcinoma	3	MONDO:0015459	MONDO:0015459
adenoid cystic carcinoma	2	MONDO:0004971	EFO:0000231
neoplasm	2	MONDO:0005070	EFO:0000616
gastrointestinal stromal tumor	2	MONDO:0011719	MONDO:0011719
head and neck squamous cell carcinoma	2	MONDO:0010150	EFO:0000181
oral cavity squamous cell carcinoma	2	MONDO:0004958	EFO:0000199
carcinoma	2	MONDO:0004993	EFO:0000313
lung adenocarcinoma	2	MONDO:0005061	EFO:0000571
neuroblastoma	2	MONDO:0005072	EFO:0000621
osteosarcoma	2	MONDO:0009807	EFO:0000637
renal cell carcinoma	2	MONDO:0005086	EFO:0000681
sarcoma	2	MONDO:0005089	EFO:0000691
squamous cell carcinoma	2	MONDO:0005096	EFO:0000707
cervical carcinoma	2	MONDO:0005131	EFO:0001061
lung carcinoma	2	MONDO:0005138	EFO:0001071
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
medulloblastoma	2	MONDO:0007959	EFO:0002939
pancreatic neoplasm	2	MONDO:0021040	EFO:0003860
biliary tract neoplasm	2	MONDO:0005304	EFO:0003891
nasopharyngeal neoplasm	2	MONDO:0005375	EFO:0004252
upper aerodigestive tract neoplasm	2	MONDO:0005398	EFO:0004284
cholangiocarcinoma	2	MONDO:0019087	EFO:0005221
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
head and neck cancer	2	MONDO:0005627	EFO:0006859
malignant pancreatic neoplasm	2	MONDO:0009831	EFO:1000359
olfactory neuroblastoma	2	MONDO:0006329	EFO:1000407
paraganglioma	2	MONDO:0000448	EFO:1000453
gallbladder carcinoma	2	MONDO:0003220	EFO:1001956
intrahepatic cholangiocarcinoma	2	MONDO:0003210	EFO:1001961
soft tissue sarcoma	2	MONDO:0018078	EFO:1001968
neuroendocrine carcinoma	2	MONDO:0002120	MONDO:0002120
lung neoplasm	2	MONDO:0021117	MONDO:0008903
colonic neoplasm	2	MONDO:0005401	MONDO:0021063
glioma	2	MONDO:0021042	MONDO:0100342
peripheral T-cell lymphoma, not otherwise specified	1	MONDO:0004964	EFO:0000211
lymphoma	1	MONDO:0005062	EFO:0000574
oral cavity neoplasm	1	MONDO:0021245	EFO:0003868

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

Clinical trials

Total trials: 444.

Phase distribution

Phase	Trials
PHASE2	290
PHASE3	43
Not specified	32
PHASE1	28
PHASE1/PHASE2	24
PHASE2/PHASE3	17
PHASE4	9
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02426034	PHASE4	COMPLETED	A Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03475589	PHASE4	UNKNOWN	Study on the Adverse Drug Reactions (ADRs) of Apatinib and Their Biomarker Correlations
NCT03631862	PHASE4	UNKNOWN	Treatment of Newly Diagnosed Peripheral T-cell Lymphoma
NCT03725423	PHASE4	UNKNOWN	Apatinib for Advanced Lung Squmamous Carcinoma
NCT03792503	PHASE4	WITHDRAWN	Pemetrexed Plus Apatinib Maintenance Treatment in Patients With Non-squamous Non-small Cell Lung Cancer Patients Who Have Not Progressed After 4 Cycles of Induction Chemotherapy of Pemetrexed in Combination With Platinum-based Regimen
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT04208347	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Perioperative Treatment of Combined SOX With Apatinib and Camrelizumab for Oesophagogastric Cancer
NCT04342910	PHASE3	RECRUITING	Study to Evaluate the Efficacy and Safety of Camrelizumab and Apatinib in Patients With GC/GEJC
NCT04521153	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Camrelizumab Combined With Apatinib Mesylate for Perioperative Treatment of Resectable Hepatocellular Carcinoma
NCT04639180	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Camrelizumab Plus Rivoceranib (Apatinib) as Adjuvant Therapy in Patients With Hepatocellular Carcinoma (HCC) at High Risk of Recurrence After Curative Resection or Ablation
NCT04803539	PHASE2/PHASE3	RECRUITING	A Prospective, Phase II Trial Using ctDNA to Initiate Post-operation Boost Therapy After Adjuvant Chemotherapy in TNBC
NCT05198609	PHASE3	ACTIVE_NOT_RECRUITING	Camrelizumab, Apatinib Plus HAIC Versus Camrelizumab and Apatinib for HCC With Portal Vein Invasion: a Randomized Trial
NCT05320692	PHASE3	ACTIVE_NOT_RECRUITING	A Study of TACE Combined With Camrelizumab Plus Rivoceranib (Apatinib) in Patients With Incurable Hepatocellular Carcinoma
NCT05613478	PHASE3	RECRUITING	Camrelizumab Combined With Apatinib Mesylate and TACE in the Perioperative Treatment of Hepatocellular Carcinoma
NCT05699655	PHASE2/PHASE3	RECRUITING	Tislelizumab Combined With Apatinib and Oxaliplatin Plus S1 Vs Oxaliplatin Plus S1 as Neoadjuvant Therapy for Borrmann IV、Large Borrmann III Type and Bulky N Positive Advanced Gastric Cancer
NCT05789043	PHASE3	RECRUITING	Camrelizumab in Combination With Apatinib and Temozolomide as First-line Treatment in Advanced Acral Melanoma
NCT05854849	PHASE3	RECRUITING	Gemcitabine and Camrelizumab Plus Apatinib Versus Cisplatin in First-line Treatment of RM-NPC
NCT06172205	PHASE3	RECRUITING	Infusional FOLFOX Plus Camrelizumab and Apatinib vs HAIC-FOLFOX Plus Camrelizumab and Apatinib for Advanced HCC
NCT06188455	PHASE3	NOT_YET_RECRUITING	Maintenance Therapy After Platinum-containing Chemotherapy in Patients With Recurrent Ovarian Cancer
NCT06255392	PHASE3	RECRUITING	Randomized, Open, Controlled, Multicenter Phase III Clinical Study of Fluzoparib in Combination With Apatinib Versus Investigator-Selected Chemotherapy for HRD-Positive/HER2-negative Advanced Breast Cancer
NCT06346392	PHASE3	ACTIVE_NOT_RECRUITING	AZD0901 Compared With Investigator’s Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2
NCT06351020	PHASE3	ACTIVE_NOT_RECRUITING	LM-302 for the Treatment of Subjects With Claudin18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma.
NCT06447623	PHASE3	RECRUITING	Apatinib Combined With cdk4/6i in First-line Treatment for HR+/HER2- SNF4 Subtype Breast Cancer
NCT06485466	PHASE3	RECRUITING	TACE Plus Camrelizumab and Apatinib for Unresectable Hepatocellular Carcinoma
NCT06539091	PHASE3	NOT_YET_RECRUITING	Fluzoparib in Combination With Apatinib Mesylate for Maintenance Therapy in Stage III-IV Ovarian Cancer
NCT06796803	PHASE2/PHASE3	NOT_YET_RECRUITING	Camrelizumab Combined with Rivoceranib and Hepatic Arterial Infusion Chemotherapy (HAIC) As Conversion Therapy for Potentially Resectable Hepatocellular Carcinoma(HCC)
NCT06889688	PHASE3	RECRUITING	Phase III Trial of Camrelizumab+Apatinib+Eribulin vs. Physician’s Choice Chemotherapy in Advanced Triple-Negative Breast Cancer
NCT07267806	PHASE3	RECRUITING	Camrelizumab and Apatinib With or Without FOLFOX Chemotherapy for Advanced HCC
NCT07309419	PHASE2/PHASE3	NOT_YET_RECRUITING	A Phase III Randomized Study of TACE Plus an Oral Triple-Agent Cocktail Versus TACE Plus First-Line Targeted Immunotherapy in Unresectable Hepatocellular Carcinoma
NCT07314203	PHASE3	NOT_YET_RECRUITING	Clinical Efficacy of Adebrelimab With or Without Apatinib Mesilate and SOX Neoadjuvant Therapy in Locally Advanced Gastric Cancer
NCT07371910	PHASE3	ACTIVE_NOT_RECRUITING	Fluorizoparib Plus Apatinib Versus Chemotherapy in HRD-positive, HER2-negative Advanced Breast Cancer
NCT07589244	PHASE2/PHASE3	RECRUITING	A Study of VRT106, Combined With Camrelizumab, and Apatinib for Advanced HCC
NCT00970138	PHASE2/PHASE3	COMPLETED	Apatinib Versus Placebo as a Third Line Treatment in Patients With Advanced or Metastatic Gastric Cancer
NCT01287962	PHASE3	UNKNOWN	Apatinib in the Treatment of Advanced Non-squamous Non-small Cell Lung Cancer
NCT01512745	PHASE3	COMPLETED	Phase III Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer
NCT02329860	PHASE3	COMPLETED	Study of Apatinib After Systemic Therapy in Patients With Hepatocellular Carcinoma(AHELP)
NCT02332512	PHASE3	UNKNOWN	Study of Apatinib as 3rd/4th Line Treatment in Patients With Advanced Non-Squamous Non-small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor (EGFR)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 7 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
ERLOTINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
FEDRATINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
PONATINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
QUIZARTINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
SORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, KIT, RET
AXITINIB	ChEMBL	Phase 4 (approved)	CSK, KDR, KIT, RET
BRIGATINIB	ChEMBL	Phase 4 (approved)	CSK, KDR, KIT, RET
DASATINIB	ChEMBL	Phase 4 (approved)	CSK, KDR, KIT, RET
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	CSK, KDR, KIT, RET
VANDETANIB	ChEMBL	Phase 4 (approved)	CSK, KDR, KIT, RET
CANERTINIB	ChEMBL	Phase 3	CSK, KDR, KIT, RET
LESTAURTINIB	ChEMBL	Phase 3	CSK, KDR, KIT, RET
SARACATINIB	ChEMBL	Phase 3	CSK, KDR, KIT, RET
DEFOSBARASERTIB	ChEMBL	Phase 2	CSK, KDR, KIT, RET
FORETINIB	ChEMBL	Phase 2	CSK, KDR, KIT, RET
R-406	ChEMBL	Phase 2	CSK, KDR, KIT, RET
REBASTINIB	ChEMBL	Phase 2	CSK, KDR, KIT, RET
TOZASERTIB	ChEMBL	Phase 2	CSK, KDR, KIT, RET
Selumetinib	PubChem	Approved	CSK, KDR, KIT, RET
IBRUTINIB	ChEMBL + PubChem	Phase 4 (approved)	CSK, KDR, RET
BOSUTINIB	ChEMBL	Phase 4 (approved)	CSK, KIT, RET
CABOZANTINIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
CERITINIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
ENTRECTINIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
INFIGRATINIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
LENVATINIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
NILOTINIB	ChEMBL	Phase 4 (approved)	CSK, KIT, RET
NINTEDANIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
SUNITINIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
TIVOZANIB	ChEMBL	Phase 4 (approved)	KDR, KIT, RET
BARASERTIB	ChEMBL	Phase 3	KDR, KIT, RET
BRIVANIB	ChEMBL	Phase 3	KDR, KIT, RET
CEDIRANIB	ChEMBL	Phase 3	KDR, KIT, RET
DOVITINIB	ChEMBL	Phase 3	KDR, KIT, RET
LINIFANIB	ChEMBL	Phase 3	KDR, KIT, RET
MOTESANIB	ChEMBL	Phase 3	KDR, KIT, RET
SEMAXANIB	ChEMBL	Phase 3	KDR, KIT, RET
VATALANIB	ChEMBL	Phase 3	KDR, KIT, RET
AT-9283	ChEMBL	Phase 2	CSK, KDR, RET
BEMCENTINIB	ChEMBL	Phase 2	KDR, KIT, RET
BFH-772	ChEMBL	Phase 2	KDR, KIT, RET
BMS-777607	ChEMBL	Phase 2	KDR, KIT, RET
CENISERTIB	ChEMBL	Phase 2	KDR, KIT, RET
CEP-32496	ChEMBL	Phase 2	KDR, KIT, RET
DANUSERTIB	ChEMBL	Phase 2	KDR, KIT, RET
DORAMAPIMOD	ChEMBL	Phase 2	KDR, KIT, RET
ENMD-2076	ChEMBL	Phase 2	KDR, KIT, RET
ILORASERTIB	ChEMBL	Phase 2	KDR, KIT, RET
RAF-265	ChEMBL	Phase 2	KDR, KIT, RET
SU-014813	ChEMBL	Phase 2	KDR, KIT, RET
Binimetinib	PubChem	Approved	CSK, KDR, RET
Idelalisib	PubChem	Approved	CSK, KIT, RET
Fostamatinib	ChEMBL + PubChem	Phase 4 (approved)	CSK, RET
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, KIT
Lapatinib	ChEMBL + PubChem	Phase 4 (approved)	CSK, RET