Inhibition of human wild-type CFTR expressed in FRT cells coexpressing YFP-H148Q assessed as inhibition of cAMP agonist-induced iodide influx after 45 mins by fluorescence plate-reader analysis - BioAssay Summary
We previously reported the discovery of pyrimido-pyrrolo-quinoxalinedione (PPQ) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in an organ culture model of polycystic kidney disease (PKD) (J. Med. Chem. 2009, 52, 6447-6455). Here, we report related benzopyrimido-pyrrolo-oxazinedione (BPO) CFTR inhibitors. To establish structure-activity relationships and select lead compound(s) with improved potency, metabolic stability, and aqueous solubility compared to the most potent prior compound 8 (PPQ-102, IC(50) # ..more
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 Tested Compounds
 Tested Compounds
All(28)
 
 
Active(22)
 
 
Inactive(6)
 
 
 Tested Substances
 Tested Substances
All(28)
 
 
Active(22)
 
 
Inactive(6)
 
 
 Related BioAssays
 Related BioAssays
Table of Contents
AID: 619073
Data Source: ChEMBL (769084)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2013-05-15

Data Table (Complete):           Active    All
Target
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Sequence: RecName: Full=Cystic fibrosis transmembrane conductance regulator; Short=CFTR; AltName: Full=ATP-binding cassette sub-family C member 7; AltName: Full=Channel conductance-controlling ATPase; AltName: Full=cAMP-dependent chloride channel
Description ..   
Protein Family: ATP-binding cassette domain of the cystic fibrosis transmembrane regulator, subfamily C
Comment ..   

Gene:CFTR     Related Protein 3D Structures
BioActive Compounds: 22
Description:
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Title: Potent, metabolically stable benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR inhibitors for polycystic kidney disease.

Abstract: We previously reported the discovery of pyrimido-pyrrolo-quinoxalinedione (PPQ) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in an organ culture model of polycystic kidney disease (PKD) (J. Med. Chem. 2009, 52, 6447-6455). Here, we report related benzopyrimido-pyrrolo-oxazinedione (BPO) CFTR inhibitors. To establish structure-activity relationships and select lead compound(s) with improved potency, metabolic stability, and aqueous solubility compared to the most potent prior compound 8 (PPQ-102, IC(50) #
(PMID: 21707078)
Comment
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Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
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ChEMBL Assay Type: Functional

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 11540

ChEMBL target type: Target is a single protein chain

Result Definitions
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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
* Activity Concentration.

Data Table (Concise)
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Classification
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