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BioAssay: AID 552680

Inhibition of recombinant ERK2 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(28)
 
 
Active(2)
 
 
Unspecified(26)
 
 
 Tested Substances
 Tested Substances
All(28)
 
 
Active(2)
 
 
Unspecified(26)
 
 
 Related BioAssays
 Related BioAssays
AID: 552680
Data Source: ChEMBL (701208)
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 Compounds: 2
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: 11638
Target Type: SINGLE PROTEIN
Pref Name: MAP kinase ERK2
Synonyms: ERK-2;ERT1;Extracellular signal-regulated kinase 2;MAP kinase 1;MAP kinase 2;MAP kinase isoform p42;MAPK 1;MAPK 2;Mitogen-activated protein kinase 1;Mitogen-activated protein kinase 2;p42-MAPK;
Gene Name: ERK2 ;MAPK1;PRKM1;PRKM2;
Protein Accession: P28482;
Protein GI: 119554;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme kinase protein kinase cmgc mapk erk
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 valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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