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BioAssay: AID 552675

Inhibition of STK3 at 10 uM 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(6)
 
 
Unspecified(6)
 
 
 Tested Substances
 Tested Substances
All(6)
 
 
Unspecified(6)
 
 
 Related BioAssays
 Related BioAssays
AID: 552675
Data Source: ChEMBL (701203)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-18
Modify Date: 2014-05-26

Data Table ( Complete ):           View All Data
Tested Compounds:
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
Putative Target:

ChEMBL Target ID: 10277
Target Type: SINGLE PROTEIN
Pref Name: Serine/threonine-protein kinase MST2
Synonyms: Mammalian STE20-like protein kinase 2;MST-2;MST2/C;MST2/N;Serine/threonine-protein kinase 3;Serine/threonine-protein kinase 3 20kDa subunit;Serine/threonine-protein kinase 3 36kDa subunit;Serine/threonine-protein kinase Krs-1;STE20-like kinase MST2;
Gene Name: KRS1 ;MST2;STK3;
Protein Accession: Q13188;
Protein GI: 46577700;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme kinase protein kinase ste ste20 mst
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat%
5Inhibition standard valueInhibition standard valueFloat%

Data Table (Concise)
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