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Brivanib

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Also known as BMS-540215CPD 12BRIVANIB (BMS-540215)BMS 540215

Summary

Brivanib (CHEMBL377300) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting FGFR1, FLT1, and KDR; indicated across 10 conditions including hepatocellular carcinoma and carcinoma.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 3 (FGFR1, FLT1, KDR)
  • Indications: 10 conditions
  • Clinical trials: 18
  • Chemistry: 370.4 Da · C19H19FN4O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL377300
NameBrivanib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID11234052
ChEBICHEBI:167686
Molecular formulaC19H19FN4O3
Molecular weight370.4
InChIKeyWCWUXEGQKLTGDX-LLVKDONJSA-N

SMILES: CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OC[C@@H](C)O)C

IUPAC name: (2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol

ChEBI definition: A secondary alcohol resulting from the hydrolysis of the carboxylic ester group of brivanib alaninate. It is a dual VEGFR-2/FGFR-1 kinase inhibitor whose alanine prodrug, brivanib alaninate is currently under development as an oral agent for the treatment of cancer.

Pharmacological roles (ChEBI): antineoplastic agent, EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, angiogenesis inhibitor, apoptosis inducer, fibroblast growth factor receptor antagonist.

Other ChEBI roles (chemical / environmental): drug metabolite.

Also known as: BMS-540215, Brivanib, BRIVANIB, CPD 12, BRIVANIB (BMS-540215), BMS 540215

Patent coverage: 727 distinct patent families (1,721 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,643 (95%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
FGFR1fibroblast growth factor receptor 1Inhibition6.8311.5%P11362
FLT1fms related receptor tyrosine kinase 1Inhibition6.420.1%P17948
KDRkinase insert domain receptorInhibition7.61.1%P35968

Broader ChEMBL bioactivity targets: 42 (assay-derived). Sample: STE20-related kinase adapter protein alpha, Macrophage colony-stimulating factor 1 receptor, Tyrosine-protein kinase ABL1, Vascular endothelial growth factor receptor 1, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Vascular endothelial growth factor receptor 3, Platelet-derived growth factor receptor alpha, Epidermal growth factor receptor, Proto-oncogene tyrosine-protein kinase receptor Ret.

Bioactivity

ChEMBL activities: 77 potent at pChembl ≥ 5 of 84 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
KDR8.3Kd5nMCHEMBL_ACT_7586145
FLT18Kd10nMCHEMBL_ACT_7586138
PDGFRA7.96Kd11nMCHEMBL_ACT_7587852
KIT7.92Kd12nMCHEMBL_ACT_7586077
KIT7.77Kd17nMCHEMBL_ACT_7586076
KDR7.6IC5025nMCHEMBL_ACT_1699775
KDR7.6IC5025nMCHEMBL_ACT_2164834
KDR7.58IC5026nMCHEMBL_ACT_15458386
KDR7.58IC5026nMCHEMBL_ACT_15462664
KDR7.58Ki26nMCHEMBL_ACT_1701293
STK357.58Kd26nMCHEMBL_ACT_7587976
FGFR17.55IC5028nMCHEMBL_ACT_15462666
FGFR17.55IC5028nMCHEMBL_ACT_15469024
P359187.55Ki28nMCHEMBL_ACT_1701768
KIT7.46Kd35nMCHEMBL_ACT_7586075
KIT7.44Kd36nMCHEMBL_ACT_7586070
PDGFRB7.3Kd50nMCHEMBL_ACT_7586160
KIT7.27Kd54nMCHEMBL_ACT_7586074
FLT47.25Kd56nMCHEMBL_ACT_7586139
FLT17.22Ki60nMCHEMBL_ACT_1701769
P359187.05IC5089nMCHEMBL_ACT_1699820
FGFR17Kd99nMCHEMBL_ACT_7587954
FGFR26.96Kd110nMCHEMBL_ACT_7587953
FGFR16.83IC50148nMCHEMBL_ACT_1699822
FGFR36.82Kd150nMCHEMBL_ACT_7586067
FGFR36.8Kd160nMCHEMBL_ACT_7586066
DDR16.8Kd160nMCHEMBL_ACT_7586135
TNIK6.8Kd160nMCHEMBL_ACT_7587913
SLK6.77Kd170nMCHEMBL_ACT_7587906
EPHA66.72Kd190nMCHEMBL_ACT_7586101

Target pathways

Aggregated over 3 target gene(s): FGFR1, FLT1, KDR.

Top Reactome pathways

29 total, by targets touching each:

PathwayTargetsGenes
Neuropilin interactions with VEGF and VEGFR2FLT1, KDR
VEGF binds to VEGFR leading to receptor dimerization2FLT1, KDR
PI3K Cascade1FGFR1
PIP3 activates AKT signaling1FGFR1
Signaling by FGFR1 amplification mutants1FGFR1
Signaling by activated point mutants of FGFR11FGFR1
FGFR1b ligand binding and activation1FGFR1
FGFR1c ligand binding and activation1FGFR1
FGFR1c and Klotho ligand binding and activation1FGFR1
Integrin cell surface interactions1KDR
Constitutive Signaling by Aberrant PI3K in Cancer1FGFR1
NCAM signaling for neurite out-growth1FGFR1
VEGFA-VEGFR2 Pathway1KDR
Signal transduction by L11FGFR1
VEGFR2 mediated cell proliferation1KDR
Phospholipase C-mediated cascade: FGFR11FGFR1
Downstream signaling of activated FGFR11FGFR1
SHC-mediated cascade:FGFR11FGFR1
PI-3K cascade:FGFR11FGFR1
FRS-mediated FGFR1 signaling1FGFR1
Negative regulation of FGFR1 signaling1FGFR1
Signaling by FGFR1 in disease1FGFR1
RAF/MAP kinase cascade1FGFR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling1FGFR1
Signaling by plasma membrane FGFR1 fusions1FGFR1
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB1KDR
Epithelial-Mesenchymal Transition (EMT) during gastrulation1FGFR1
Formation of paraxial mesoderm1FGFR1
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells1KDR

Dominant GO biological processes

GO termTargets
angiogenesis3
protein phosphorylation3
positive regulation of cell population proliferation3
cell migration3
peptidyl-tyrosine phosphorylation3
positive regulation of MAPK cascade3
protein autophosphorylation3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction3
positive regulation of mesenchymal cell proliferation2
mesenchymal cell proliferation2
positive regulation of MAP kinase activity2
positive regulation of blood vessel endothelial cell migration2
calcium ion homeostasis2
stem cell proliferation2
positive regulation of stem cell proliferation2

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).

IndicationTrial phaseMONDOEFO
hepatocellular carcinoma3MONDO:0007256EFO:0000182
carcinoma3MONDO:0004993EFO:0000313
colorectal adenocarcinoma2MONDO:0005008EFO:0000365
colorectal neoplasm2MONDO:0005335MONDO:0005575
neoplasm1MONDO:0005070EFO:0000616
ovarian cancer1MONDO:0008170MONDO:0008170

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

Clinical trials

Total trials: 18.

Phase distribution

PhaseTrials
PHASE19
PHASE34
PHASE24
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00825955PHASE3COMPLETEDComparison of Brivanib and Best Supportive Care to Placebo for Treatment of Liver Cancer for Those Subjects Who Have Failed Sorafenib Treatment
NCT00858871PHASE3COMPLETEDFirst Line Hepato Cellular Carcinoma (HCC)
NCT00908752PHASE3COMPLETEDPhase III Trans-Arterial Chemo-Embolization (TACE) Adjuvant HCC
NCT01108705PHASE3TERMINATEDComparison of Brivanib and Best Supportive Care (BSC) With Placebo and BSC for Treatment of Liver Cancer in Asian Patients Who Have Failed Sorafenib Treatment
NCT00355238PHASE2COMPLETEDA Phase II Open Label Study of BMS-582664 in Locally Advanced or Metastatic Hepatocellular Cancer
NCT00594984PHASE1/PHASE2COMPLETEDPhase I/II Combination With Irinotecan- Erbitux
NCT00633789PHASE2COMPLETEDPhase II Study of Brivanib (BMS-582664) to Treat Multiple Tumor Types
NCT01367275PHASE2TERMINATEDIrinotecan Plus Brivanib in Metastatic Colorectal Cancer (CRC) Enriched for Elevated Levels of Plasma FGF
NCT03516071PHASE2COMPLETEDA Phase 2 Study of Brivanib in Chinese Patients With Previously Treated Advanced HCC
NCT00207051PHASE1COMPLETEDBMS-582664 in Combination With Erbitux in Patients With Advanced Gastrointestinal Malignancies
NCT00207103PHASE1COMPLETEDMAD in Cancer Patients: Safety of BMS-582664 in Patients With Advanced or Metastatic Solid Tumors
NCT00390936PHASE1COMPLETEDA Study of BMS-582664 in Patients With Advanced or Metastatic Solid Tumors
NCT00435669PHASE1COMPLETEDA Phase I Study to Determine Absorption, Distribution, Metabolism, and Elimination of a Single Radiolabeled Dose of Brivanib (BMS-582664)
NCT00437424PHASE1COMPLETEDA Study of Brivanib (BMS-582664) in Patients With Liver Cancer and Mild, Moderate or Severe Liver Dysfunction
NCT00437437PHASE1COMPLETEDA Phase I Study to Determine the Effect of Food on Brivanib (BMS-582664)
NCT01046864PHASE1COMPLETEDCombination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)
NCT01540461PHASE1COMPLETEDDetermine the Pharmacokinetics and Safety of Brivanib in Chinese Subjects With Advanced Primary Liver Cancer (Hepatocellular Carcinoma: HCC)
NCT03895788PHASE1UNKNOWNA Study of Niraparib in Combination With Brivanib in Recurrent Ovarian Cancer

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.

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.

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

MoleculeSourceStatusShared targets
CrizotinibChEMBL + PubChemPhase 4 (approved)FGFR1, FLT1, KDR
GefitinibChEMBL + PubChemPhase 4 (approved)FGFR1, FLT1, KDR
PAZOPANIBChEMBL + PubChemPhase 4 (approved)FGFR1, FLT1, KDR
REGORAFENIBChEMBL + PubChemPhase 4 (approved)FGFR1, FLT1, KDR
AXITINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
CABOZANTINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
DASATINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
ENTRECTINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
FEDRATINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
INFIGRATINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
LENVATINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
MIDOSTAURINChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
NINTEDANIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
NINTEDANIB ESYLATEChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
PONATINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
SORAFENIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
SUNITINIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
TIVOZANIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
VANDETANIBChEMBLPhase 4 (approved)FGFR1, FLT1, KDR
ALISERTIBChEMBLPhase 3FGFR1, FLT1, KDR
CEDIRANIBChEMBLPhase 3FGFR1, FLT1, KDR
DOVITINIBChEMBLPhase 3FGFR1, FLT1, KDR
LESTAURTINIBChEMBLPhase 3FGFR1, FLT1, KDR
LINIFANIBChEMBLPhase 3FGFR1, FLT1, KDR
MOTESANIBChEMBLPhase 3FGFR1, FLT1, KDR
ORANTINIBChEMBLPhase 3FGFR1, FLT1, KDR
SEMAXANIBChEMBLPhase 3FGFR1, FLT1, KDR
SURUFATINIBChEMBLPhase 3FGFR1, FLT1, KDR
AT-9283ChEMBLPhase 2FGFR1, FLT1, KDR
CENISERTIBChEMBLPhase 2FGFR1, FLT1, KDR
CEP-11981ChEMBLPhase 2FGFR1, FLT1, KDR
DORAMAPIMODChEMBLPhase 2FGFR1, FLT1, KDR
FORETINIBChEMBLPhase 2FGFR1, FLT1, KDR
ILORASERTIBChEMBLPhase 2FGFR1, FLT1, KDR
LUCITANIBChEMBLPhase 2FGFR1, FLT1, KDR
MK-2461ChEMBLPhase 2FGFR1, FLT1, KDR
OSI-632ChEMBLPhase 2FGFR1, FLT1, KDR
R-406ChEMBLPhase 2FGFR1, FLT1, KDR
RAF-265ChEMBLPhase 2FGFR1, FLT1, KDR
REBASTINIBChEMBLPhase 2FGFR1, FLT1, KDR
SU-014813ChEMBLPhase 2FGFR1, FLT1, KDR
TANDUTINIBChEMBLPhase 2FGFR1, FLT1, KDR
TOZASERTIBChEMBLPhase 2FGFR1, FLT1, KDR
AfatinibPubChemApprovedFGFR1, FLT1, KDR
SelumetinibPubChemApprovedFGFR1, FLT1, KDR
BRIGATINIBChEMBLPhase 4 (approved)FGFR1, KDR
ERDAFITINIBChEMBLPhase 4 (approved)FGFR1, KDR
ERLOTINIBChEMBLPhase 4 (approved)FLT1, KDR
FRUQUINTINIBChEMBLPhase 4 (approved)FLT1, KDR
FUTIBATINIBChEMBLPhase 4 (approved)FGFR1, KDR
NICLOSAMIDEChEMBLPhase 4 (approved)FGFR1, KDR
PEXIDARTINIBChEMBLPhase 4 (approved)FLT1, KDR
QUIZARTINIBChEMBLPhase 4 (approved)FLT1, KDR
UPADACITINIBChEMBLPhase 4 (approved)FGFR1, KDR
CANERTINIBChEMBLPhase 3FLT1, KDR
CEP-1347ChEMBLPhase 3FLT1, KDR
DEFACTINIBChEMBLPhase 3FLT1, KDR
VATALANIBChEMBLPhase 3FLT1, KDR
AEE-788ChEMBLPhase 2FLT1, KDR
AG-13958ChEMBLPhase 2FGFR1, KDR

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot