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BioAssay: AID 551814

Inhibition of MCP1-mediated human THP cell migration

Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in the primary ROCK-I IMAP assay. Compounds 23A and 23E were selected as fragment more ..
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 Tested Compounds
 Tested Compounds
All(4)
 
 
Active(3)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Active(3)
 
 
Unspecified(1)
 
 
AID: 551814
Data Source: ChEMBL (700342)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-18
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=C-C motif chemokine 2; AltName: Full=HC11; AltName: Full=Monocyte chemoattractant protein 1; AltName: Full=Monocyte chemotactic and activating factor; Short=MCAF; AltName: Full=Monocyte chemotactic protein 1; Short=MCP-1; AltName: Full=Monocyte secretory protein JE; AltName: Full=Small-inducible cytokine A2; Flags: Precursor
Description ..   
Protein Family: Chemokine_CC
Comment ..   

Gene:CCL2     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 3
Description:
Title: Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors.

Abstract: Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in the primary ROCK-I IMAP assay. Compounds 23A and 23E were selected as fragment optimized hits for further profiling. Compound 23A has similar ROCK-1 affinity, potency and cell based efficacy to the first generation ROCK inhibitors, however, it has a superior PK profile in C57 mouse. Compound 23E demonstrates the feasibility of improving ROCK-1 affinity, potency and cell based efficacy for the series, however, it has a poor PK profile relative to 23A.
(PMID: 21145740)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloat
10IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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