Bookmark and Share
BioAssay: AID 262725

Inhibitory activity against Flk1

A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a substituted alkoxy group at the 6-position of the pyrrolo[2,1-f][1,2,4]triazine core gave potent compounds. Biochemical potency, kinase more ..
_
   
 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 262725
Data Source: ChEMBL (342121)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2013-11-18

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Vascular endothelial growth factor receptor 2; Short=VEGFR-2; AltName: Full=Fetal liver kinase 1; Short=FLK-1; AltName: Full=Kinase NYK; AltName: Full=Protein-tyrosine kinase receptor flk-1; AltName: CD_antigen=CD309; Flags: Precursor
Description ..   
Protein Family: Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2
Comment ..   

Gene:KDR     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor.

Abstract: A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor-2 kinase is reported. Structure-activity relationship studies revealed that a methyl group at the 5-position and a substituted alkoxy group at the 6-position of the pyrrolo[2,1-f][1,2,4]triazine core gave potent compounds. Biochemical potency, kinase selectivity, and pharmacokinetics of the series were optimized and in vitro safety liabilities were minimized to afford BMS-540215 (12), which demonstrated robust preclinical in vivo activity in human tumor xenograft models. The l-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors.
(PMID: 16570908)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 12469

ChEMBL Target Type: Target is a single protein chain

Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM
7IC50 binding domainsIC50 binding domainsString
8IC50 Binding Efficiency Index(nM)IC50 Binding Efficiency Index(nM)Float
9IC50 Surface Efficiency Index(nM)IC50 Surface Efficiency Index(nM)Float
10IC50 Ligand EfficiencyIC50 Ligand EfficiencyFloat
11IC50 Lipophilic Ligand EfficiencyIC50 Lipophilic Ligand EfficiencyFloat
12Ki activity commentKi activity commentString
13Ki standard flagKi standard flagInteger
14Ki qualifierKi qualifierString
15Ki published valueKi published valueFloatnM
16Ki standard valueKi standard valueFloatnM
17Ki binding domainsKi binding domainsString
18Ki Binding Efficiency Index(nM)Ki Binding Efficiency Index(nM)Float
19Ki Surface Efficiency Index(nM)Ki Surface Efficiency Index(nM)Float
20Ki Ligand EfficiencyKi Ligand EfficiencyFloat
21Ki Lipophilic Ligand EfficiencyKi Lipophilic Ligand EfficiencyFloat

* Activity Concentration.

Data Table (Concise)
Classification
PageFrom: