This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Semaxanib
Accession Number
DB06436
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
NSC-696819 / SU-5416 / SU005416 / SU5416
Categories
UNII
71IA9S35AJ
CAS number
194413-58-6
Weight
Average: 238.2845
Monoisotopic: 238.11061308
Chemical Formula
C15H14N2O
InChI Key
WUWDLXZGHZSWQZ-WQLSENKSSA-N
InChI
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-
IUPAC Name
(3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one
SMILES
CC1=CC(C)=C(N1)\C=C1/C(=O)NC2=CC=CC=C12

Pharmacology

Indication

Investigated for use/treatment in colorectal cancer and lung cancer.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UVascular endothelial growth factor receptor 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Semaxanib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Semaxanib.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Semaxanib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Semaxanib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Semaxanib.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Semaxanib.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Semaxanib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Semaxanib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Semaxanib.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Semaxanib.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Semaxanib.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Semaxanib.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Semaxanib.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Semaxanib.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Semaxanib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Semaxanib.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Semaxanib.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Semaxanib.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Semaxanib.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
5329098
PubChem Substance
347827770
ChemSpider
4486260
BindingDB
4810
ChEBI
91083
ChEMBL
CHEMBL276711
HET
X2M
Wikipedia
Semaxanib
PDB Entries
2x2m

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAbdominal wall neoplasm / Cancer, Ovarian / Fallopian Tube Neoplasms1
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentHead and Neck Carcinoma1
1CompletedTreatmentProstate Cancer1
1CompletedTreatmentSarcomas1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific3
1TerminatedTreatmentBrain and Central Nervous System Tumors1
1Unknown StatusTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentAdenocarcinoma of the Colon / Adenocarcinoma of the Rectum / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage III Colon Cancer / Stage III Rectal Cancer / Stage IV Colon Cancer / Stage IV Rectal Cancer1
1, 2CompletedTreatmentBrain and Central Nervous System Tumors1
1, 2CompletedTreatmentChronic Myelomonocytic Leukemia / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation1
1, 2CompletedTreatmentSarcomas2
2CompletedTreatmentCarcinoma of Unknown Primary / Head and Neck Carcinoma / Non-Melanomatous Skin Cancer1
2CompletedTreatmentCervical Cancers1
2CompletedTreatmentGastrointestinal Stromal Tumors / Sarcomas1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentMelanoma (Skin)1
2CompletedTreatmentMesothelioma, Malignant1
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRenal Cancers1
2CompletedTreatmentSarcomas1
2TerminatedTreatmentColorectal Cancers1
2TerminatedTreatmentRecurrent Melanoma / Stage IV Melanoma1
2TerminatedTreatmentRecurrent Renal Cell Cancer / Stage IV Renal Cell Cancer1
3CompletedTreatmentColorectal Cancers1
3Unknown StatusTreatmentColorectal Cancers1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.104 mg/mLALOGPS
logP2.64ALOGPS
logP2.98ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)11.29ChemAxon
pKa (Strongest Basic)-2.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area44.89 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity74.56 m3·mol-1ChemAxon
Polarizability26.98 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9738
Caco-2 permeable+0.5838
P-glycoprotein substrateNon-substrate0.6258
P-glycoprotein inhibitor INon-inhibitor0.7324
P-glycoprotein inhibitor IINon-inhibitor0.9313
Renal organic cation transporterNon-inhibitor0.8624
CYP450 2C9 substrateNon-substrate0.849
CYP450 2D6 substrateNon-substrate0.8516
CYP450 3A4 substrateSubstrate0.5093
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorNon-inhibitor0.5121
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8183
Ames testNon AMES toxic0.5485
CarcinogenicityNon-carcinogens0.9303
BiodegradationNot ready biodegradable0.9956
Rat acute toxicity2.4908 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9818
hERG inhibition (predictor II)Non-inhibitor0.8521
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolines
Direct Parent
Indolines
Alternative Parents
Substituted pyrroles / Benzenoids / Heteroaromatic compounds / Secondary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Dihydroindole / Substituted pyrrole / Benzenoid / Pyrrole / Heteroaromatic compound / Secondary carboxylic acid amide / Lactam / Carboxamide group / Azacycle / Carboxylic acid derivative
show 9 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Fury MG, Zahalsky A, Wong R, Venkatraman E, Lis E, Hann L, Aliff T, Gerald W, Fleisher M, Pfister DG: A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers. Invest New Drugs. 2007 Apr;25(2):165-72. Epub 2006 Sep 16. [PubMed:16983506]
  2. Mita MM, Rowinsky EK, Forero L, Eckhart SG, Izbicka E, Weiss GR, Beeram M, Mita AC, de Bono JS, Tolcher AW, Hammond LA, Simmons P, Berg K, Takimoto C, Patnaik A: A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2007 Feb;59(2):165-74. Epub 2006 May 31. [PubMed:16736151]
  3. Hoff PM, Wolff RA, Bogaard K, Waldrum S, Abbruzzese JL: A Phase I study of escalating doses of the tyrosine kinase inhibitor semaxanib (SU5416) in combination with irinotecan in patients with advanced colorectal carcinoma. Jpn J Clin Oncol. 2006 Feb;36(2):100-3. Epub 2006 Jan 31. [PubMed:16449240]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Sakao S, Taraseviciene-Stewart L, Cool CD, Tada Y, Kasahara Y, Kurosu K, Tanabe N, Takiguchi Y, Tatsumi K, Kuriyama T, Voelkel NF: VEGF-R blockade causes endothelial cell apoptosis, expansion of surviving CD34+ precursor cells and transdifferentiation to smooth muscle-like and neuronal-like cells. FASEB J. 2007 Nov;21(13):3640-52. Epub 2007 Jun 13. [PubMed:17567571]

Drug created on March 19, 2008 10:33 / Updated on November 09, 2017 03:54