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Details

Stereochemistry ACHIRAL
Molecular Formula C15H14N2O
Molecular Weight 238.2845
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SEMAXANIB

SMILES

CC1=CC(C)=C(N1)\C=C2/C(=O)NC3=C2C=CC=C3

InChI

InChIKey=WUWDLXZGHZSWQZ-WQLSENKSSA-N
InChI=1S/C15H14N2O/c1-9-7-10(2)16-14(9)8-12-11-5-3-4-6-13(11)17-15(12)18/h3-8,16H,1-2H3,(H,17,18)/b12-8-

HIDE SMILES / InChI

Molecular Formula C15H14N2O
Molecular Weight 238.2845
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00009919 | https://clinicaltrials.gov/ct2/show/NCT00023725 | https://clinicaltrials.gov/ct2/show/NCT00006003 | https://clinicaltrials.gov/ct2/show/NCT00004252

Semaxanib is a potent and selective vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 inhibitor that also inhibits other tyrosine kinases KIT, MET, FLT3, and RET. Semaxanib inhibited cell migration of human vascular endothelial cells expressing both Flt-1 and KDR in response to VEGF and also inhibited the cell migration in response to placenta growth factor (PIGF), a specific ligand for Flt-1. Chemotaxis of monocytes expressing only Flt-1 was also inhibited by SU5416 in a dose-dependent manner. Semaxanib targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential. On February 2002, Pharmacia, the then-parent of Sugen, prematurely ended Phase III clinical trials of Semaxinib in the treatment of advanced colorectal cancer due to discouraging results.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
190 mg/m2 2 times / week multiple, intravenous (unknown)
Highest studied dose
Dose: 190 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 190 mg/m2, 2 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: advanced malignancies
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
DLT: vomiting, headache...
Dose limiting toxicities:
vomiting
headache (severe)
Sources:
AEs

AEs

AESignificanceDosePopulation
vomiting DLT
190 mg/m2 2 times / week multiple, intravenous (unknown)
Highest studied dose
Dose: 190 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 190 mg/m2, 2 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: advanced malignancies
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
headache severe
DLT
190 mg/m2 2 times / week multiple, intravenous (unknown)
Highest studied dose
Dose: 190 mg/m2, 2 times / week
Route: intravenous
Route: multiple
Dose: 190 mg/m2, 2 times / week
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: advanced malignancies
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis.
2000 Jun 15
SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes.
2003 Aug 1
SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway.
2004 Nov 12
Vascular endothelial growth factor in diabetes induced early retinal abnormalities.
2004 Sep
Vascular endothelial growth factor: a therapeutic target for tumors of the Ewing's sarcoma family.
2005 Mar 15
Vascular endothelial growth factor and hepatocyte regeneration in acetaminophen toxicity.
2006 Jul
A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma.
2007 Feb
Impaired VEGF and nitric oxide signaling after nitrofen exposure in rat fetal lung explants.
2008 Jan
TSU-16, (Z)-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a potent activator of aryl hydrocarbon receptor and increases CYP1A1 and CYP1A2 expression in human hepatocytes.
2010 Apr 15
Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats.
2010 Sep 1
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
2011 Oct 30
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013 Apr 15
Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway.
2013 Mar
Bromodomain-Containing Protein 4: The Epigenetic Origin of Pulmonary Arterial Hypertension.
2015 Aug 28
Patents

Patents

Sample Use Guides

145 mg/m2 intravenously twice-weekly in combination with thalidomide, commencing at 200 mg daily with intrapatient dose escalation as tolerated
Route of Administration: Intravenous
Cells (HMEC-1, BAEC, HELA or MCF-7) were seeded in 48-well plates at 10,000 cells per cm2. After 16 h, the cells were incubated in fresh medium in the presence of the test compounds (Semaxanib 1-100mkM). On day 4, (BAEC, HELA, MCF-7) or day 7 (HMEC-1) cells were trypsinized and counted by means of a Coulter counter (Analis, Belgium). For each compound, the IC50 value was determined.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:46:32 UTC 2023
Edited
by admin
on Fri Dec 15 15:46:32 UTC 2023
Record UNII
71IA9S35AJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SEMAXANIB
INN   MART.   USAN   WHO-DD  
INN   USAN  
Official Name English
2H-INDOL-2-ONE, 3-(3,5-DIMETHYL-1H-PYRROL-2-YL)METHYLENE)- 1,3-DIHYDRO-,(Z)-
Common Name English
semaxanib [INN]
Common Name English
NSC-696819
Code English
SU-5416
Code English
(3Z)-3-((3,5-DIMETHYL-1H-PYRROL-2-YL)METHYLIDENE)-1,3-DIHYDRO-2H-INDOL-2-ONE
Systematic Name English
Semaxanib [WHO-DD]
Common Name English
SEMAXANIB [USAN]
Common Name English
SU005416
Code English
SU5416
Code English
SEMAXANIB [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
FDA ORPHAN DRUG 116398
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
FDA ORPHAN DRUG 127699
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C1831
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
SMS_ID
100000124388
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
EVMPD
SUB32269
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
INN
8004
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
EPA CompTox
DTXSID801025708
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
NSC
696819
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
CAS
194413-58-6
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
CHEBI
91083
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
PUBCHEM
5329098
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
WIKIPEDIA
SEMAXANIB
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
DRUG BANK
DB06436
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
FDA UNII
71IA9S35AJ
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
USAN
KK-118
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
MESH
C116890
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
ChEMBL
CHEMBL276711
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY