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BioAssay: AID 552681

Inhibition of recombinant p38alpha after 60 mins by TR-FRET assay

In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38I+/- and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-I ..more
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 Tested Compounds
 Tested Compounds
All(29)
 
 
Active(1)
 
 
Unspecified(28)
 
 
 Tested Substances
 Tested Substances
All(29)
 
 
Active(1)
 
 
Unspecified(28)
 
 
 Related BioAssays
 Related BioAssays
AID: 552681
Data Source: ChEMBL (701209)
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
BioActive Compound: 1
Description:
Title: Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration.

Abstract: In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38I+/- and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-I
(PMID: 21112785)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 10188
Target Type: SINGLE PROTEIN
Pref Name: MAP kinase p38 alpha
Synonyms: CSAID-binding protein;CSBP;Cytokine suppressive anti-inflammatory drug-binding protein;MAP kinase 14;MAP kinase MXI2;MAP kinase p38 alpha;MAPK 14;MAX-interacting protein 2;Mitogen-activated protein kinase 14;Mitogen-activated protein kinase p38 alpha;SAPK2a;Stress-activated protein kinase 2a;
Gene Name: CSBP ;CSBP1;CSBP2;CSPB1;MAPK14;MXI2;SAPK2A;
Protein Accession: Q16539;
Protein GI: 2499600;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme kinase protein kinase cmgc mapk p38
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
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 valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 activity commentIC50 activity commentString
12IC50 standard flagIC50 standard flagInteger
13IC50 qualifierIC50 qualifierString
14IC50 published valueIC50 published valueFloatμM
15IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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