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c-Jun N-Terminal Kinase (JNK) Inhibitor
No.175(October 2017)
SP600125 (1) is an inhibitor for JNK1, JNK2, and JNK3 with IC50 of 40 nM, 40 nM, and 90 nM respectively.1) Inhibitory constants of 1 for these JNKs are Ki = 0.19 μM. The inhibitory mechanism of 1 to the JNKs is ATP-competitive.
The selectivity of 1 was determined by crystal structural analysis using the ternary complex, JNK1-peptide fragment JIP1-1.2) JIP1 is a member of the JNK-interacting protein (JIP) family and contains a JNK binding domain (JBD), an SRC homology (SH3) domain, and a phosphotyrosine-binding (PTB) domain.3,4) JBD possesses the consensus sequence, R/KXXXXLXL.5) The sequence of peptide fragment JIP1 used in the research described above is RPKRPTTLNLF.2)
References
- 1)SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
- 2)Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
- 3)A mammalian scaffold complex that selectively mediates MAP kinase activation
- 4)Scaffold proteins of MAP-kinase modules
- 5)Differential targeting of MAP kinases to the ETS-domain transcription factor Elk-1
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