Brief Description

GSK2656157 is an ATP-competitive inhibitor of PERK enzyme activity with an IC(50) of 0.9 nM; is highly selective for PERK with IC50 values >100 nM against a panel of 300 kinases.
IC50 value: 0.9 nM
Target: PERK
in vitro: GSK2656157 inhibits PERK activity in cells with an IC(50) in the range of 10-30 nmol/L as shown by inhibition of stress-induced PERK autophosphorylation, eIF2α substrate phosphorylation, together with corresponding decreases in ATF4 and CAAT/enhancer binding protein homologous protein (CHOP) in multiple cell lines. inhibition of PERK activity by GSK2656157 does not always correlate with inhibition of eIF2α phosphorylation. Also, GSK2656157 does not always mimic the biological effects of the genetic inactivation of PERK. Furthermore, cells treated with GSK2656157 increase eIF2α phosphorylation as a means to compensate for the loss of PERK.
in vivo: Oral administration of GSK2656157 to mice shows a dose- and time-dependent pharmacodynamic response in pancreas as measured by PERK autophosphorylation. Twice daily dosing of GSK2656157 results in dose-dependent inhibition of multiple human tumor xenografts growth in mice. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect.

Solubility

DMSO

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Light yellow solid