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BioAssay: AID 613654

Penetration ratio, ratio of AUC (0 to 4 hrs) in Sprague-Dawley rat CSF to AUC (0 to 4 hrs) in Sprague-Dawley rat unbound plasma at 3.2 mg/kg, sc

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: 613654
Data Source: ChEMBL (763665)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-05-26

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
Assay Type: ADME

Assay Data Source: Scientific Literature

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ratio AUC activity commentRatio AUC activity commentString
2Ratio AUC standard flagRatio AUC standard flagInteger
3Ratio AUC qualifierRatio AUC qualifierString
4Ratio AUC published valueRatio AUC published valueFloat
5Ratio AUC standard valueRatio AUC standard valueFloat

Data Table (Concise)
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