GAK Inhibitor

A cell-permeable isothiazolopyridine based compound that acts as a high-affinity binding, reversible and ATP-competitive inhibitor of cyclin G associated kinase (GAK; K_d = 8.3 nM). Displays moderate to excellent selectivity over Kit, PDGFRβ, Flt3, Mek5 & PDGFRα (K_d = 29, 70, 110, 150 & 220 nM, respectively) in a 456-kinase profiling. Shown to dose-dependently disrupt both HCV entry & assembly and efficiently arrest HCV infection (EC₅₀ = 2.55 & 3.6 µM in HCVcc- & HCVpp-infected Huh-7.5 cells, respectively; CC₅₀ = 23.27 µM in HCVcc-infected Huh-7.5 cells). Significantly inhibits intracellular & extracellular infectivity (EC₅₀ = 1.64 & 2.13 µM, respectively) and AP2M1 phosphorylation. Exerts no effect on HCV RNA replication.

Cell permeable: yes

Primary Target
GAK

Reversible: yes

Secondary Target
Kit, PDGFRβ, Flt3, Mek5 & PDGFRα

Packaged under inert gas

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

Kovackova, S., et al. 2015. J. Med. Chem.58, 3393.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)