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BioAssay: AID 692205

Inhibition of human delta-5 desaturase activity expressed in human HEpG2 cells

The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing more ..
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 Tested Compounds
 Tested Compounds
All(5)
 
 
Unspecified(5)
 
 
 Tested Substances
 Tested Substances
All(5)
 
 
Unspecified(5)
 
 
 Related BioAssays
 Related BioAssays
AID: 692205
Data Source: ChEMBL (852949)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-05-24

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Fatty acid desaturase 1; AltName: Full=Delta(5) fatty acid desaturase; Short=D5D; Short=Delta(5) desaturase; Short=Delta-5 desaturase
Description ..   
Comment ..   

Gene:FADS1     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia.

Abstract: The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ believed to be responsible for the therapeutic efficacy (liver) while minimizing its exposure in the tissues associated with mechanism-based SCD depletion of essential lubricating lipids (skin and eye). These efforts led to the discovery of MK-8245 (7), a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window.
(PMID: 21661758)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
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 valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM
7IC50 data validityIC50 data validityString

* Activity Concentration.

Data Table (Concise)
Classification
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