Merck, 5387700001, GAK Inhibitor

General description
A cell-permeable isothiazolopyridine based compound that acts as a high-affinity binding, reversible and ATP-competitive inhibitor of cyclin G associated kinase (GAK; Kd = 8.3 nM). Displays moderate to excellent selectivity over Kit, PDGFRβ, Flt3, Mek5 & PDGFRα (Kd = 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.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
GAK
Reversible: yes
Secondary Target
Kit, PDGFRβ, Flt3, Mek5 & PDGFRα
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Kovackova, S., et al. 2015. J. Med. Chem.58, 3393.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)