SEMAXANIB

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16736151
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12477352	Inhibitor 8297	43.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24890652	Inhibitor 8297	12.9 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12477352	Inhibitor 8297	50.0 nM [IC50]
Stem cell growth factor receptor 53 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12477352	Inhibitor 8297	35.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Colorectal cancer 101 Sources: https://clinicaltrials.gov/ct2/show/NCT00021281	Primary	Phase III 656	Unknown Approved Use Unknown
Recurrent renal cell cancer 1 Sources: https://clinicaltrials.gov/ct2/show/record/NCT00009919	Primary	Phase II 1132	Unknown Approved Use Unknown
Recurrent melanoma 2 Sources: https://clinicaltrials.gov/ct2/show/record/NCT00006003	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/16222321	unhealthy, ADULT Health Status: unhealthy Condition: advanced malignancies Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16222321	DLT: vomiting, headache... Dose limiting toxicities: vomiting headache (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/16222321

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/16222321	unhealthy, ADULT Health Status: unhealthy Condition: advanced malignancies Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16222321
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: https://pubmed.ncbi.nlm.nih.gov/16222321	unhealthy, ADULT Health Status: unhealthy Condition: advanced malignancies Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16222321

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY103036	https://www.001chemical.com/chem/search?q=DY103036
1PlusChem LLC	1P0029PK	https://www.1pchem.com/search?query=1P0029PK
1PlusChem LLC	1P00AD2C	https://www.1pchem.com/search?query=1P00AD2C
AChemBlock	R16021	http://www.achemblock.com/catalogsearch/result/?q=R16021
AK Scientific	2033AH	https://aksci.com/item_detail.php?cat=2033AH
AK Scientific	SYN5667	https://aksci.com/item_detail.php?cat=SYN5667
AOBIOUS INC	AOB6828	http://aobious.com/aobious/search?search_query=AOB6828
Ambeed	A325242	http://www.ambeed.com/search/Search.html?keyword=A325242
Angene	AGN-PC-0JLO6Y	http://www.angenechemical.com/productshow/AGN-PC-0JLO6Y.html
Angene	AGN-PC-0WH8XN	http://www.angenechemical.com/productshow/AGN-PC-0WH8XN.html
ApexBio Technology	A3847	https://www.apexbt.com/catalogsearch/result/?q=A3847
AstaTech	N11132	http://astatechinc.com/CPSResult.php?CRNO=N11132
BLD Pharm	BD304613	http://www.bldpharm.com/search/Search.html?keyword=BD304613
BLD Pharm	BD304645	http://www.bldpharm.com/search/Search.html?keyword=BD304645
BOC Sciences	204005-46-9	http://www.bocsci.com/description.asp?cas=204005-46-9
Cayman Chemical	13342	http://www.caymanchem.com/app/template/Product.vm/catalog/13342
Chem Scene	CS-1225	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1225
ChemShuttle	101035	https://www.chemshuttle.com/catalogsearch/result/?q=101035
Combi-Blocks	QJ-8211	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-8211
Debye Scientific	DA-43377	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-43377
Excenen	EX-A2158	http://www.excenen.com/searchresultlist.php?id=EX-A2158
KeyOrganics	ES-0010	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=ES-0010
Lab Network	LN00334705	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00334705
Lab Network	LN02195801	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02195801
Lab Seeker	SC-96714	http://www.labseeker.com/search.php?keywords=SC-96714&category=0
LabSeeker	SC-96714	http://www.labseeker.com/search.php?keywords=SC-96714&category=0
Matrix Scientific	120693	http://www.matrixscientific.com/120693.html
MedChem Express	HY-10374	https://www.medchemexpress.com/search.html?q=HY-10374&ft=&fa=&fp=
MolPort	MolPort-003-959-606	https://www.molport.com/shop/molecule-link/MolPort-003-959-606
Molcore	MC103036	http://www.molcore.com/CatMC103036.html
Molnova	M13045	https://www.molnova.com/en/serch-list.html?keywords=M13045
Molnova	M13170	https://www.molnova.com/en/serch-list.html?keywords=M13170
MuseChem	I002575	https://www.musechem.com/product/I002575.html
Princeton BioMolecular Research	PBMR221869	http://www.princetonbio.com/order_online?common_id=PBMR221869
Ryan Scientific	Hygromycin_B	https://ryansci.com/products?q=Hygromycin_B&list_q=&search_type=exact
Selleck Chemicals	S2845	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2845
ShangHai Biochempartner	BCP000660	http://www.biochempartner.com/search_BCP000660
ShangHai Biochempartner	BCP06068	http://www.biochempartner.com/search_BCP06068
Tocris	3037	https://www.tocris.com/search.php?Type=QuickSearch&Value=3037
Toronto Research Chemicals	S688030	https://www.trc-canada.com/product-detail/?CatNum=S688030
W&J PharmaChem	50C626116	http://wjpharmachem.com/new/searcht.php?keyword=50C626116
eMolecules	23139179	https://orderbb.emolecules.com/search/#?query=23139179
eMolecules	48885056	https://orderbb.emolecules.com/search/#?query=48885056
eMolecules	50524609	https://orderbb.emolecules.com/search/#?query=50524609
eNovation Chemicals	D480364	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D480364&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D509216	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D509216&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1878399527	https://mcule.com/MCULE-1878399527/
mcule	MCULE-9309817841	https://mcule.com/MCULE-9309817841/

PubMed

Title	Date	PubMed
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	10882357
Phase II study of SU5416--a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor--in patients with refractory myeloproliferative diseases.	2003 Apr 15	12673719
SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes.	2003 Aug 1	12649163
SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway.	2004 Nov 12	15474452
Vascular endothelial growth factor in diabetes induced early retinal abnormalities.	2004 Sep	15331199
Vascular endothelial growth factor: a therapeutic target for tumors of the Ewing's sarcoma family.	2005 Mar 15	15788688
Vascular endothelial growth factor and hepatocyte regeneration in acetaminophen toxicity.	2006 Jul	16565415
Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension.	2006 Oct	16698853
A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma.	2007 Feb	16736151
Effects of vascular endothelial growth factor receptor inhibitor SU5416 and prostacyclin on murine lung metastasis.	2007 Mar	17264769
Impaired VEGF and nitric oxide signaling after nitrofen exposure in rat fetal lung explants.	2008 Jan	17993583
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	20171196
Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats.	2010 Sep 1	20508210
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362
Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway.	2013 Mar	22983702
Bromodomain-Containing Protein 4: The Epigenetic Origin of Pulmonary Arterial Hypertension.	2015 Aug 28	26224795

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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Name

Type

Language

SEMAXANIB

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