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BioAssay: AID 613667

Metabolic stability in dog liver microsomes assessed as hepatic extraction ratio

By use of parallel chemistry coupled with physicochemical property design, a series of selective kappa opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro kappa antagonism were confirmed in the tail-flick analgesia model. This model was used to build an more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 613667
Data Source: ChEMBL (763678)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2013-07-07

Data Table ( Complete ):           All
Tested Compound:
Description:
Title: Design and discovery of a selective small molecule kappa opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).

Abstract: By use of parallel chemistry coupled with physicochemical property design, a series of selective kappa opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro kappa antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the kappa K(i) and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.
(PMID: 21744827)
Comment
Putative Target:

ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment
ChEMBL Assay Type: ADMET

ChEMBL Assay Data Source: Scientific Literature

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1ERH activity commentERH activity commentString
2ERH standard flagERH standard flagInteger
3ERH qualifierERH qualifierString
4ERH published valueERH published valueFloat
5ERH standard valueERH standard valueFloat

Data Table (Concise)
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