Motesanib

Summary

Motesanib (CHEMBL572881) is a phase-3 clinical-stage small molecule targeting FLT1, KDR, and FLT4; indicated across 2 conditions including non-small cell lung carcinoma and breast neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (FLT1, KDR, FLT4)
• Indications: 2 conditions
• Clinical trials: 2
• Chemistry: 373.5 Da · C22H23N5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL572881
Name	Motesanib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11667893
ChEBI	CHEBI:51098
Molecular formula	C22H23N5O
Molecular weight	373.5
InChIKey	RAHBGWKEPAQNFF-UHFFFAOYSA-N

SMILES: CC1(CNC2=C1C=CC(=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4)C

IUPAC name: N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide

Also known as: AMG 706, AMG-706, Motesanib, MOTESANIB, SID137276049, motesanib

Parent form; salt/anhydrous children: CHEMBL2107357

Patent coverage: 1,687 distinct patent families (4,642 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,447 (74%) 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	8.7	0.1%	P17948
KDR	kinase insert domain receptor	Inhibition	8.52	1.1%	P35968
FLT4	fms related receptor tyrosine kinase 4	Inhibition	8.22	0.2%	P35916

Broader ChEMBL bioactivity targets: 46 (assay-derived). Sample: Receptor-interacting serine/threonine-protein kinase 3, Tyrosine-protein kinase Fyn, Macrophage colony-stimulating factor 1 receptor, Tyrosine-protein kinase ABL1, Vascular endothelial growth factor receptor 1, RAF proto-oncogene serine/threonine-protein kinase, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Vascular endothelial growth factor receptor 3, Receptor-type tyrosine-protein kinase FLT3.

Bioactivity

ChEMBL activities: 144 potent at pChembl ≥ 5 of 144 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MAP4K1	9	Kd	1	nM	CHEMBL_ACT_17913444
KIT	8.89	Kd	1.3	nM	CHEMBL_ACT_7589592
FLT1	8.7	IC50	2	nM	CHEMBL_ACT_12138543
FLT1	8.7	IC50	2	nM	CHEMBL_ACT_16610764
FLT1	8.7	IC50	2	nM	CHEMBL_ACT_23289738
FLT1	8.7	IC50	2	nM	CHEMBL_ACT_26212346
KDR	8.52	IC50	3	nM	CHEMBL_ACT_12138542
KDR	8.52	IC50	3	nM	CHEMBL_ACT_16610765
GSPT2	8.52	Kd	3	nM	CHEMBL_ACT_17905539
KDR	8.52	IC50	3	nM	CHEMBL_ACT_23289713
KDR	8.52	IC50	3	nM	CHEMBL_ACT_26212347
KDR	8.52	Ki	3	nM	CHEMBL_ACT_27790673
KDR	8.52	IC50	3	nM	CHEMBL_ACT_3595758
KIT	8.49	Kd	3.2	nM	CHEMBL_ACT_2897022
KIT	8.49	Kd	3.2	nM	CHEMBL_ACT_7589593
KIT	8.43	Kd	3.7	nM	CHEMBL_ACT_2895922
KIT	8.43	Kd	3.7	nM	CHEMBL_ACT_6220449
KIT	8.43	Kd	3.7	nM	CHEMBL_ACT_7589588
CSF1R	8.25	Kd	5.6	nM	CHEMBL_ACT_2902371
CSF1R	8.25	Kd	5.6	nM	CHEMBL_ACT_7591332
FLT4	8.22	IC50	6	nM	CHEMBL_ACT_12138541
FLT4	8.22	IC50	6	nM	CHEMBL_ACT_23289721
P35918	8.22	IC50	6	nM	CHEMBL_ACT_26212348
FLT4	8.22	IC50	6	nM	CHEMBL_ACT_26212349
KIT	8.1	IC50	8	nM	CHEMBL_ACT_26212351
MAP3K20	8.1	Kd	8	nM	CHEMBL_ACT_2891586
MAP3K20	8.1	Kd	8	nM	CHEMBL_ACT_7591498
PDGFRB	8.04	Kd	9.1	nM	CHEMBL_ACT_2899064
PDGFRB	8.04	Kd	9.1	nM	CHEMBL_ACT_7589678
FLT4	8.01	Kd	9.7	nM	CHEMBL_ACT_2890882

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

2 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
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
breast neoplasm	1	MONDO:0021100	MONDO:0007254

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02629848	PHASE3	TERMINATED	Study of Motesanib (AMG 706) in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer
NCT01349088	PHASE1/PHASE2	WITHDRAWN	Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast 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.

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
FRUQUINTINIB	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
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