CMK

• CAT Number: I004974
• CAS Number: 821794-90-5
• Molecular Formula: C18H19ClN4O2
• Molecular Weight: 358.83
• Purity: ≥95%
• Synonyms: 1-[4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-6-yl]-2-chloroethanone
• Target: Ribosomal S6 Kinase (RSK)
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• InChI: InChI=1S/C18H19ClN4O2/c1-11-3-5-12(6-4-11)14-15-17(20)21-10-22-18(15)23(7-2-8-24)16(14)13(25)9-19/h3-6,10,24H,2,7-9H2,1H3,(H2,20,21,22)
• InChIKey: PELFTNQHGSITLB-UHFFFAOYSA-N
• SMILES: CC1=CC=C(C=C1)C2=C(N(C3=NC=NC(=C23)N)CCCO)C(=O)CCl

CMK (Cat.No:I004974) is an inhibitor of RSK2 kinase. It has shown potent activity in inhibiting the growth of Cdc5 (L158G) with an IC50 of 36nM. CMK also induces cell cycle arrest and delays anaphase spindle migration in the cdc5-as1 strain. Further research is needed to explore its potential therapeutic applications.

Reference

[1]. Cohen, Michael S.; Zhang, Chao; Shokat, Kevan M.; Taunton, Jack. Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors.Science (Washington, DC, United States)(2005), 308(5726), 1318-1321.
Abstract
The active sites of 491 human protein kinase domains are highly conserved, which makes the design of selective inhibitors a formidable challenge. We used a structural bioinformatics approach to identify two selectivity filters, a threonine and a cysteine, at defined positions in the active site of p90 ribosomal protein S6 kinase (RSK). A fluoromethylketone inhibitor, designed to exploit both selectivity filters, potently and selectively inactivated RSK1 and RSK2 in mammalian cells. Kinases with only one selectivity filter were resistant to the inhibitor, yet they became sensitized after genetic introduction of the second selectivity filter. Thus, two amino acids that distinguish RSK from other protein kinases are sufficient to confer inhibitor sensitivity.