Semaxanib

Summary

Semaxanib (CHEMBL276711) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting PDGFRB, KIT, and FLT1; indicated across 18 conditions including colorectal adenocarcinoma and colorectal neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (PDGFRB, KIT, FLT1…)
• Indications: 18 conditions
• Clinical trials: 31
• Chemistry: 238.28 Da · C15H14N2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL276711
Name	Semaxanib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5329098
ChEBI	CHEBI:91083
Molecular formula	C15H14N2O
Molecular weight	238.28
InChIKey	WUWDLXZGHZSWQZ-WQLSENKSSA-N

SMILES: CC1=CC(=C(N1)/C=C\2/C3=CC=CC=C3NC2=O)C

IUPAC name: (3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one

ChEBI definition: An oxindole that is 3-methyleneoxindole in which one of the hydrogens of the methylene group is replaced by a 3,5-dimethylpyrrol-2-yl group.

Pharmacological roles (ChEBI): antineoplastic agent, vascular endothelial growth factor receptor antagonist, EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, angiogenesis modulating agent.

Also known as: NSC-696819, Semaxanib, Su-5416, SU-5416, SU005416, SU5416, Semaxinib, semaxanib, semaxinib, SID49674962, SID50107014, SID50107016

Patent coverage: 2,202 distinct patent families (6,180 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,108 (66%) 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
PDGFRB	platelet derived growth factor receptor beta	Inhibition	6.17	2.3%	P09619
KIT	KIT proto-oncogene, receptor tyrosine kinase	Inhibition	6.4	0.5%	P10721
FLT1	fms related receptor tyrosine kinase 1	Inhibition	8.1	0.1%	P17948
KDR	kinase insert domain receptor	Inhibition	6.7	1.1%	P35968

Broader ChEMBL bioactivity targets: 36 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Microtubule-associated protein tau, Ubiquitin carboxyl-terminal hydrolase 2, Prelamin-A/C, ATP-dependent DNA helicase Q1, RecQ-like DNA helicase BLM, 4’-phosphopantetheinyl transferase ffp, NPC intracellular cholesterol transporter 1, Geminin, Peripheral myelin protein 22.

Bioactivity

ChEMBL activities: 55 potent at pChembl ≥ 5 of 101 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
FLT1	8.1	IC50	8	nM	CHEMBL_ACT_1147930
KIT	7.46	IC50	35	nM	CHEMBL_ACT_1175362
KDR	7.4	IC50	40	nM	CHEMBL_ACT_526969
FLT1	7.37	IC50	43	nM	CHEMBL_ACT_1175341
FLT1	7.37	IC50	43	nM	CHEMBL_ACT_15731028
FLT4	7.3	IC50	50	nM	CHEMBL_ACT_1175343
PDGFRB	7.17	IC50	68	nM	CHEMBL_ACT_15731001
PDGFRB	7.17	IC50	68	nM	CHEMBL_ACT_3418609
CSF1R	7.08	IC50	84	nM	CHEMBL_ACT_1175346
KDR	6.96	IC50	110	nM	CHEMBL_ACT_3064712
FLT3	6.8	IC50	160	nM	CHEMBL_ACT_25482357
FLT3	6.8	IC50	160	nM	CHEMBL_ACT_3101486
RET	6.77	IC50	170	nM	CHEMBL_ACT_3101521
KDR	6.7	IC50	200	nM	CHEMBL_ACT_1147931
PDGFRA	6.7	IC50	200	nM	CHEMBL_ACT_12697474
KDR	6.7	IC50	200	nM	CHEMBL_ACT_1897071
KDR	6.66	IC50	220	nM	CHEMBL_ACT_1175342
KDR	6.66	IC50	220	nM	CHEMBL_ACT_15731019
KDR	6.66	IC50	220	nM	CHEMBL_ACT_3418608
KDR	6.64	IC50	230	nM	CHEMBL_ACT_1494140
KIT	6.4	IC50	400	nM	CHEMBL_ACT_1147933
PDGFRB	6.4	IC50	400	nM	CHEMBL_ACT_12697473
FLT4	6.3	IC50	500	nM	CHEMBL_ACT_12697475
MEN1	6.3	Potency	501.2	nM	CHEMBL_ACT_3618872
KIT	6.18	IC50	660	nM	CHEMBL_ACT_1175345
PDGFRB	6.17	IC50	680	nM	CHEMBL_ACT_1147932
KDR	6.16	IC50	700	nM	CHEMBL_ACT_526965
KDR	6.16	IC50	700	nM	CHEMBL_ACT_92599
KDR	6.05	IC50	884	nM	CHEMBL_ACT_1175355
KDR	6.03	ED50	930	nM	CHEMBL_ACT_1147934

Target pathways

Aggregated over 4 target gene(s): PDGFRB, KIT, FLT1, KDR.

Top Reactome pathways

48 total, by targets touching each:

Pathway	Targets	Genes
PIP3 activates AKT signaling	2	KIT, PDGFRB
Neuropilin interactions with VEGF and VEGFR	2	FLT1, KDR
VEGF binds to VEGFR leading to receptor dimerization	2	FLT1, KDR
Constitutive Signaling by Aberrant PI3K in Cancer	2	KIT, PDGFRB
RAF/MAP kinase cascade	2	KIT, PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	KIT, PDGFRB
Developmental Biology	1	KIT
Signaling by SCF-KIT	1	KIT
Regulation of KIT signaling	1	KIT
Signal Transduction	1	KIT
Disease	1	KIT
Downstream signal transduction	1	PDGFRB
Signaling by PDGF	1	PDGFRB
Negative regulation of the PI3K/AKT network	1	KIT
Generic Transcription Pathway	1	KIT
Integrin cell surface interactions	1	KDR
PI3K/AKT Signaling in Cancer	1	KIT
VEGFA-VEGFR2 Pathway	1	KDR
VEGFR2 mediated cell proliferation	1	KDR
Diseases of signal transduction by growth factor receptors and second messengers	1	KIT
MAPK family signaling cascades	1	KIT
MAPK1/MAPK3 signaling	1	KIT
RNA Polymerase II Transcription	1	KIT
Gene expression (Transcription)	1	KIT
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	KIT
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	KIT
Intracellular signaling by second messengers	1	KIT
Signaling by Receptor Tyrosine Kinases	1	KIT
Dasatinib-resistant KIT mutants	1	KIT
Imatinib-resistant KIT mutants	1	KIT

Dominant GO biological processes

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

Indications & clinical

Indications

18 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 adenocarcinoma	3	MONDO:0005008	EFO:0000365
colorectal neoplasm	3	MONDO:0005335	MONDO:0005575
renal cell carcinoma	2	MONDO:0005086	EFO:0000681
mesothelioma	2	MONDO:0005065	EFO:0000588
melanoma	2	MONDO:0005105	EFO:0000756
cutaneous melanoma	2	MONDO:0005012	EFO:0000389
sarcoma	2	MONDO:0005089	EFO:0000691
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
kidney cancer	2	MONDO:0002367	MONDO:0002367
plasma cell neoplasm	2	MONDO:0004959	EFO:0000200
neoplasm	1	MONDO:0005070	EFO:0000616
head and neck cancer	1	MONDO:0005627	EFO:0006859
central nervous system neoplasm	1	MONDO:0006130	EFO:1000158
rectal cancer	1	MONDO:0006519	EFO:1000657
breast neoplasm	1	MONDO:0021100	MONDO:0007254
colonic neoplasm	1	MONDO:0005401	MONDO:0021063

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

Clinical trials

Total trials: 31.

Phase distribution

Phase	Trials
PHASE2	13
PHASE1	10
PHASE1/PHASE2	5
PHASE3	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00004252	PHASE3	COMPLETED	Leucovorin and Fluorouracil With or Without SU5416 in Treating Patients With Metastatic Colorectal Cancer
NCT00021281	PHASE3	UNKNOWN	Combination Chemotherapy With or Without SU5416 in Treating Patients With Metastatic Colorectal Cancer
NCT00004868	PHASE1/PHASE2	COMPLETED	SU5416 in Treating Patients With Recurrent Astrocytoma or Mixed Glioma That Has Not Responded to Radiation Therapy
NCT00005042	PHASE2	COMPLETED	SU5416 in Treating Patients With AIDS-Related Kaposi’s Sarcoma
NCT00005818	PHASE1/PHASE2	COMPLETED	SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer
NCT00005862	PHASE2	COMPLETED	SU5416 in Treating Patients With Advanced, Metastatic, or Recurrent Soft Tissue Sarcomas
NCT00005931	PHASE2	COMPLETED	SU5416 in Patients With AIDS-Related Kaposi’s Sarcoma Who Have Not Responded to Treatment
NCT00005942	PHASE1/PHASE2	COMPLETED	Liposomal Daunorubicin and SU5416 in Treating Patients With Hematologic Cancer That Has Not Responded to Initial Therapy
NCT00006001	PHASE2	TERMINATED	SU5416 in Treating Patients With Metastatic or Locally Recurrent Colorectal Cancer
NCT00006002	PHASE2	COMPLETED	SU5416 Compared to Dexamethasone in Treating Patients With Progressive Prostate Cancer That Has Not Responded to Hormone Therapy
NCT00006003	PHASE2	TERMINATED	SU5416 in Treating Patients With Metastatic Melanoma That Has Been Previously Treated
NCT00006013	PHASE2	COMPLETED	SU5416 in Treating Patients With Refractory or Relapsed Multiple Myeloma
NCT00006014	PHASE2	COMPLETED	SU5416 in Treating Patients With Malignant Mesothelioma
NCT00006361	PHASE2	COMPLETED	SU5416 in Treating Patients With Advanced or Recurrent Cancer of the Head and Neck
NCT00006384	PHASE2	COMPLETED	SU5416 and Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Kidney Cancer
NCT00009919	PHASE2	TERMINATED	SU5416 in Treating Patients With Metastatic Kidney Cancer That Has Not Responded to Previous Treatment
NCT00017316	PHASE2	COMPLETED	Thalidomide and SU5416 in Treating Patients With Metastatic Melanoma
NCT00023725	PHASE1/PHASE2	COMPLETED	Radiation Therapy With or Without SU5416 in Treating Patients With Soft Tissue Sarcoma
NCT00023738	PHASE1/PHASE2	COMPLETED	Chemotherapy, SU5416, Radiation Therapy, and Surgery in Treating Patients With Soft Tissue Sarcoma
NCT00026260	PHASE2	COMPLETED	SU5416 in Treating Patients With Persistent or Recurrent Cervical Cancer
NCT00003720	PHASE1	COMPLETED	SU5416 in Treating Patients With AIDS-Related Kaposi’s Sarcoma
NCT00005642	PHASE1	COMPLETED	SU5416 in Treating Patients With Advanced Solid Tumors
NCT00005647	PHASE1	COMPLETED	SU5416 and Paclitaxel in Treating Patients With Recurrent, Locally Advanced or Metastatic Cancer of the Head and Neck
NCT00005822	PHASE1	COMPLETED	SU5416 and Doxorubicin in Treating Patients With Stage IIIB or Stage IV Inflammatory Breast Cancer
NCT00005996	PHASE1	UNKNOWN	SU5416 Combined With Gemcitabine and Cisplatin in Treating Patients With Advanced Solid Tumors
NCT00006000	PHASE1	COMPLETED	SU5416, Irinotecan, and Cisplatin in Treating Patients With Advanced Solid Tumors
NCT00006155	PHASE1	COMPLETED	SU5416 and Carboplatin to Treat Ovarian Cancer
NCT00006247	PHASE1	TERMINATED	SU5416 in Treating Children With Recurrent or Progressive Brain Tumors
NCT00006257	PHASE1	COMPLETED	SU5416 and Paclitaxel in Treating Patients With Advanced Cancer
NCT00026377	PHASE1	COMPLETED	SU5416 Plus Hormone Therapy and Radiation Therapy in Treating Patients With Prostate Cancer
NCT00002226	Not specified	COMPLETED	Safety and Effectiveness of Giving SU5416 to HIV-Infected Patients With AIDS-Related Kaposi’s Sarcoma

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.

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

Molecule	Source	Status	Shared targets
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
AXITINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
DASATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
ERLOTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
FEDRATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
LENVATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
NINTEDANIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
PONATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
QUIZARTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
SORAFENIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
SUNITINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
TIVOZANIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
VANDETANIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT, PDGFRB
BRIVANIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
CANERTINIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
CEDIRANIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
DOVITINIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
LESTAURTINIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
LINIFANIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
MOTESANIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
VATALANIB	ChEMBL	Phase 3	FLT1, KDR, KIT, PDGFRB
BFH-772	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
CENISERTIB	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
CEP-32496	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
DEFOSBARASERTIB	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
DORAMAPIMOD	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
FORETINIB	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
ILORASERTIB	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
R-406	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
RAF-265	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
SU-014813	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
TANDUTINIB	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
TOZASERTIB	ChEMBL	Phase 2	FLT1, KDR, KIT, PDGFRB
Afatinib	PubChem	Approved	FLT1, KDR, KIT, PDGFRB
Selumetinib	PubChem	Approved	FLT1, KDR, KIT, PDGFRB
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	FLT1, KDR, KIT
IMATINIB	ChEMBL + PubChem	Phase 4 (approved)	KDR, KIT, PDGFRB
CABOZANTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT
ENTRECTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT
INFIGRATINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR, KIT
NINTEDANIB ESYLATE	ChEMBL	Phase 4 (approved)	FLT1, KDR, PDGFRB
BARASERTIB	ChEMBL	Phase 3	KDR, KIT, PDGFRB
FAMITINIB	ChEMBL	Phase 3	KDR, KIT, PDGFRB
ORANTINIB	ChEMBL	Phase 3	FLT1, KDR, PDGFRB
SARACATINIB	ChEMBL	Phase 3	KDR, KIT, PDGFRB
AEE-788	ChEMBL	Phase 2	FLT1, KDR, PDGFRB
LUCITANIB	ChEMBL	Phase 2	FLT1, KDR, PDGFRB
MK-2461	ChEMBL	Phase 2	FLT1, KDR, PDGFRB
OSI-632	ChEMBL	Phase 2	FLT1, KDR, PDGFRB
REBASTINIB	ChEMBL	Phase 2	FLT1, KDR, KIT
TELATINIB	ChEMBL	Phase 2	KDR, KIT, PDGFRB
Idelalisib	PubChem	Approved	FLT1, KIT, PDGFRB
BOSUTINIB	ChEMBL	Phase 4 (approved)	KIT, PDGFRB
BRIGATINIB	ChEMBL	Phase 4 (approved)	KDR, KIT
CERITINIB	ChEMBL	Phase 4 (approved)	KDR, KIT
FRUQUINTINIB	ChEMBL	Phase 4 (approved)	FLT1, KDR