Brivanib Alaninate

Summary

Brivanib Alaninate (CHEMBL270995) is a phase-3 clinical-stage small-molecule antineoplastic agent; indicated across 6 conditions including colorectal neoplasm and renal cell carcinoma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Indications: 6 conditions
• Clinical trials: 6
• Chemistry: 441.5 Da · C22H24FN5O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL270995
Name	Brivanib Alaninate
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11154925
ChEBI	CHEBI:167656
Molecular formula	C22H24FN5O4
Molecular weight	441.5
InChIKey	LTEJRLHKIYCEOX-OCCSQVGLSA-N

SMILES: CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OC[C@@H](C)OC(=O)[C@H](C)N)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-yl] (2S)-2-aminopropanoate

ChEBI definition: A carboxylic ester resulting from the formal condensation of the carboxy group of L-alanine with the hydroxy group of brivanib. It is a prodrug of brivanib (BMS-540215), a potent oral dual inhibitor of VEGFR-2 and FGFR-1 (IC50 of 25 nM and 148 nM, respectively) and was in development for the treatment of hepatocellular and colon carcinomas.

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

Also known as: Alaninate de brivanib, Alaninato de brivanib, BMS-582664, Brivanib alaninate, Brivanib l-alanine ester, BRIVANIB ALANINATE, Brivanib_alaninate, BRIVANIB ALANINATE (BMS-582664), Brivanib alaninate (BMS-582664), BRIVANIB-ALANINATE, Brivanib Alaninate

Parent form; salt/anhydrous children: CHEMBL3526472

Patent coverage: 510 distinct patent families (1,077 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 920 (85%) 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

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Platelet-derived growth factor receptor beta, Proto-oncogene tyrosine-protein kinase receptor Ret, Fibroblast growth factor receptor 1, Serine/threonine-protein kinase 10, STE20-like serine/threonine-protein kinase, Epithelial discoidin domain-containing receptor 1, NUAK family SNF1-like kinase 2, Mitogen-activated protein kinase kinase kinase kinase 4.

Bioactivity

ChEMBL activities: 7 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NUAK2	8.52	Kd	3	nM	CHEMBL_ACT_17922765
DDR1	5.98	Kd	1039	nM	CHEMBL_ACT_17896002
PDGFRB	5.72	Kd	1892	nM	CHEMBL_ACT_17924668
FGFR1	5.41	Kd	3896	nM	CHEMBL_ACT_17903198
RET	5.13	Kd	7483	nM	CHEMBL_ACT_17935032
STK10	5.07	Kd	8443	nM	CHEMBL_ACT_17940573
SLK	5.02	Kd	9488	nM	CHEMBL_ACT_17939244

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

6 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
colorectal neoplasm	3	MONDO:0005335	MONDO:0005575
renal cell carcinoma	2	MONDO:0005086	EFO:0000681
cervical carcinoma	2	MONDO:0005131	EFO:0001061
neoplasm	1	MONDO:0005070	EFO:0000616
hepatocellular carcinoma	1	MONDO:0007256	EFO:0000182

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

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE2	3
PHASE1	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00640471	PHASE3	COMPLETED	Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer
NCT00888173	PHASE2	COMPLETED	Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer
NCT01253668	PHASE2	TERMINATED	Brivanib Metastatic Renal Cell Carcinoma
NCT01267253	PHASE2	COMPLETED	Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer
NCT00300027	PHASE1	TERMINATED	Study of BMS-582664 in Combination With Either FOLFIRI or FOLFOX for Gastrointestinal (GI) Malignancies
NCT00798252	PHASE1	COMPLETED	Ascending Multiple-Dose Study of Brivanib Alaninate in Combination With Chemotherapeutic Agents in Subjects With Advanced Cancers

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

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).