Cdc2-Like Kinase Inhibitor IV, KH-CB19

A cell-permeable N-methylindolyl-enaminonitrile that acts as a more potent inhibitor than TG003 (Cat. No. 219479) against CLK1 activity (IC₅₀ = 19.7 and 48.6 nM, respectively) by targeting the kinase ATP binding site in a non-ATP mimetic fashion. KH-CB19 is also reported to exhibit higher potency than TG003 against DYRK1A (IC₅₀ = 55.2 vs. 156.1 nM, respectively) and CLK3 (IC₅₀ = 0.53 vs. >4 µM, respectively), while exhibiting no activity against a panel of 71 other protein kinases. Thermostability shift assay reveals stronger interaction of KH-CB19 toward CLK4 than CLK1, predicting better or at least comparable potency against CLK4. KH-CB19 is shown to be more effective than TG003 in suppressing both basal and TNF-α-stimulated phosphorylation of serine/arginine rich proteins SRp55 (77.5% vs. 45% inhibition by 5 µM respective inhibitor against stimulated level) and SRp75 (80% vs. 27.5% inhibition by 5 µM respective inhibitor against stimulated level), as well as human tissue factor spliced variants, flTF and asHTF, mRNA levels in human microvascular endothelial cells HMEC-1.

A cell-permeable N-methylindolyl-enaminonitrile that acts as a potent inhibitor against CLK1, DYRK1A (IC₅₀ = 19.7 and 55.2 nM, respectively), and likely CLK4, while exhibiting much lower potency against CLK3 (IC₅₀ = 0.53 µM) and little activity toward a panel of 71 other protein kinases. Shown to be more effective than TG003 (Cat. No. 219479) in suppressing both basal and TNF-α-stimulated SRp55 and SRp75 phosphorylation, as well as human tissue factor spliced variants, flTF and asHTF, mRNA levels in human microvascular endothelial cells HMEC-1 (5 to 10 µM).

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Fedorov, O., et al. 2011. Chem. Biol.18, 67.

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