A cell-permeable cyanoacrylamide compound that acts as a potent, reversible, and selective inhibitor of ribosomal S6 kinase 2 (RSK2; IC50 = 12 and 2.5nM for wild-type and T493M RSK2, respectively). Shown to act by covalently modifying Cys436 at the ATP-binding site. Exhibits good selectivity over NEK2 and PLK1 (IC50 = 530nM and 2.2uM) and does not affect the activity of a panel of 26 other protein kinases. Also shown to block phosphorylation of mitogen and stress activated kinases (MSK) 1, 2, and 3 in PMA-stimulated COS7 cells (IC50 ~100nM) and CREB phosphorylation in PMA- or UV-stimulated HeLa cells (IC50 ~300nM).
Synonyms: (E)-2-Cyano-N-(1-hydroxy-2-methylpropan-2-yl)-3-(3-(3,4,5-trimethoxyphenyl)-1H-indazol-5-yl)acrylamide, RMM46, RSK Inhibitor IV
Primary Target:RSK2
Primary Target IC50:12 and 2.5nM for wild-type and T493M RSK2, respectively
Secondary Target:MSK 1, 2, 3
Molecular Formula:C₂₄H₂₆N₄O₅
Solubility:DMSO
Purity:≥98% (HPLC)
Form:Supplied as a yellow solid.
Storage and Stability:May be stored at 4°C for short-term only. Long-term storage is recommended at -20°C. Stable for 1 year after receipt. Protect from light. For maximum recovery of product, centrifuge the original vial prior to removing the cap.
