Identification

Name
OSI-930
Accession Number
DB05913
Type
Small Molecule
Groups
Investigational
Description

OSI-930 is an orally active inhibitor of two clinically validated targets: c-Kit and the vascular endothelial growth factor receptor-2 (VEGFR-2). OSI-930 is designed to target both cancer cell proliferation and blood vessel growth (angiogenesis) in selected tumors. In preclinical studies, OSI-930 shows broad efficacy in tumor models representative of small cell lung cancer, glioblastoma, colorectal, renal, head and neck, non-small cell lung cancer and gastric cancers.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
G1PEG5Q9Y2
CAS number
Not Available
Weight
Average: 443.44
Monoisotopic: 443.09153243
Chemical Formula
C22H16F3N3O2S
InChI Key
FGTCROZDHDSNIO-UHFFFAOYSA-N
InChI
InChI=1S/C22H16F3N3O2S/c23-22(24,25)30-16-7-5-15(6-8-16)28-21(29)20-19(10-12-31-20)27-13-14-9-11-26-18-4-2-1-3-17(14)18/h1-12,27H,13H2,(H,28,29)
IUPAC Name
3-{[(quinolin-4-yl)methyl]amino}-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide
SMILES
FC(F)(F)OC1=CC=C(NC(=O)C2=C(NCC3=CC=NC4=CC=CC=C34)C=CS2)C=C1

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

Pharmacodynamics
Not Available
Mechanism of action

OSI-930 is a multi-targeted tyrosine kinase inhibitor that is designed to act as a potent co-inhibitor of the receptor tyrosine kinases c-Kit and VEGFR-2. The inhibition of the tyrosine kinase activity of Kit is expected to result in reduced cancer cell proliferation and increased cellular apoptosis in tumor types driven by Kit, resulting in inhibition of tumor growth. OSI-930 is also capable of inhibiting VEGFR-2. This receptor is present on endothelial cells and is a key mediator of blood vessel growth in response to the angiogenic growth factor VEGF. This pathway is believed to be the single most important mechanism for recruitment of new blood vessels in nearly all solid tumors. Inhibition of this pathway should therefore impact the growth and metastases of a wide range of angiogenesis-dependent malignancies.

TargetActionsOrganism
UMast/stem cell growth factor receptor KitNot AvailableHuman
UVascular endothelial growth factor receptor 1Not 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
Not Available
Food Interactions
Not Available

References

General References
  1. Garton AJ, Crew AP, Franklin M, Cooke AR, Wynne GM, Castaldo L, Kahler J, Winski SL, Franks A, Brown EN, Bittner MA, Keily JF, Briner P, Hidden C, Srebernak MC, Pirrit C, O'Connor M, Chan A, Vulevic B, Henninger D, Hart K, Sennello R, Li AH, Zhang T, Richardson F, Emerson DL, Castelhano AL, Arnold LD, Gibson NW: OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 2006 Jan 15;66(2):1015-24. [PubMed:16424037]
  2. Petti F, Thelemann A, Kahler J, McCormack S, Castaldo L, Hunt T, Nuwaysir L, Zeiske L, Haack H, Sullivan L, Garton A, Haley JD: Temporal quantitation of mutant Kit tyrosine kinase signaling attenuated by a novel thiophene kinase inhibitor OSI-930. Mol Cancer Ther. 2005 Aug;4(8):1186-97. [PubMed:16093434]
External Links
PubChem Compound
9868037
PubChem Substance
347827749
ChemSpider
8043728
BindingDB
50356877
ChEBI
91433
ChEMBL
CHEMBL1614710

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Solid Tumors2

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 Solubility0.000411 mg/mLALOGPS
logP5.12ALOGPS
logP6.41ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area63.25 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity110.28 m3·mol-1ChemAxon
Polarizability42.18 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Aromatic anilides
Alternative Parents
Quinolines and derivatives / Thiophene carboxamides / Phenoxy compounds / Phenol ethers / 2-heteroaryl carboxamides / Secondary alkylarylamines / Aralkylamines / Pyridines and derivatives / Aminothiophenes / Vinylogous amides
show 11 more
Substituents
Aromatic anilide / Quinoline / 2-heteroaryl carboxamide / Phenoxy compound / Thiophene carboxamide / Thiophene carboxylic acid or derivatives / Phenol ether / Secondary aliphatic/aromatic amine / Aralkylamine / Aminothiophene
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da

Drug created on November 18, 2007 11:28 / Updated on November 02, 2018 06:13