5.04651

GSK2656157

≥98% (HPLC), powder, PERK inhibitor, Calbiochem^®

• Synonyme(s) : PERK Inhibitor II, GSK2656157, BRK Inhibitor II, EIF2AK1 Inhibitor II, EIF2AK2 Inhibitor III, EIF2AK3 Inhibitor II, HRI Inhibitor II, MEKK2 Inhibitor I, PKR Inhibitor III, PKR-like ER Kinase Inhibitor II
• Formule empirique (notation de Hill): C₂₃H₂₁FN₆O
• Numéro CAS: 1337532-29-2
• Poids moléculaire : 416.45
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• product name: PERK Inhibitor II, GSK2656157,
• Pureté: ≥98% (HPLC)
• Niveau de qualité: 100
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: white
• Solubilité: DMSO: 100 mg/mL
• Température de stockage: −20°C

Description

Description générale

A cell-permeable pyrrolopyrimidinamine compound that acts as a potent, ATP-competitive EIF2AK3/PERK inhibitor (IC₅₀ = 0.9 nM; [ATP] = 10 µM), displaying ≥511-fold selectivity over HRI/EIF2AK1, BRK, PKR/EIF2AK2, and MEKK2 (IC₅₀ = 460, 822, 905, and 954 nM, respectively) and much reduced or little activity toward more than 300 other kinases. Potently prevents ER stress-induced enhancement of PERK and eIF2α phosphorylation as well as ATF4 & CHOP upregulation in human BxPC3 and murine LL/2 cultures in vitro (IC₅₀ ≤30 nM; 1 h drug preincubation prior to 6 h 1 µM Thapsigargin treatment, Cat. No. 586005) and exhibits antitumor efficacy against 3 pancreas and 1 multiple myeloma xenografts in mice (54-110% tumor growth inhibition; 150 mg/kg/12 h via p.o.) in vivo. More selective than GSK2606414 (Cat. No. 516535).

A cell-permeable pyrrolopyrimidinamine compound that acts as a potent, ATP-competitive EIF2AK3/PERK inhibitor (IC₅₀ = 0.9 nM; [ATP] = 10 µM), displaying ≥511-fold selectivity over HRI/EIF2AK1, BRK, PKR/EIF2AK2, and MEKK2 (IC₅₀ = 460, 822, 905, and 954 nM, respectively) and much reduced or little activity toward more than 300 other kinases. While GSK2656157 potently inhibits ER stress-induced enhancement of PERK and eIF2α phosphorylation as well as ATF4 & CHOP upregulation in human PxBC3 and murine LL/2 cultures in vitro (IC₅₀ ≤30 nM; 1 h drug preincubation prior to 6 h ER-stress induction by 1 µM Thapsigargin, Cat. No. 586005), only basal PERK phosphorylation, but not basal eIF2α phosphorylation or ATF4 & CHOP expression, is seen inhibited in pancreas (by >95% up to 8 h post single 50 mg/kg oral dose) and tumor tissues upon GSK2656157 administration in mice in vivo, resulting in the observed antitumor efficacy (54-110% tumor growth inhibition; 150 mg/kg/12 h via p.o.) and reversible pancreas damage (44% and 95% of control pancreas mass, respectively, 1 d and 15 d post 14 d 150 mg/kg/12 h oral dosing). Comparing to its structural analog GSK2606414 (Cat. No. 516535), GSK2656157 exhibits much reduced potency toward Aurora B, MLK2/MAP3K10, MLCK2/MYLK2, c-MER (IC₅₀ = 1.259, 2.796, 3.039, and 3.431 µM, respectively), c-Kit, and DDR2 (69.84% and 25.41% inhibition, respectively, at 10 µM)

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
PERK

Reversible: yes

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Regulatory Review (Z)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Use only fresh DMSO for reconstitution.

Autres remarques

Atkins, C., et al. 2013. Cancer Res.73, 1993.

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable