5.04651

GSK2656157

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

• Sinonimo/i: 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
• Formula empirica (notazione di Hill): C₂₃H₂₁FN₆O
• Numero CAS: 1337532-29-2
• Peso molecolare: 416.45
• Numero MDL: MFCD27997885
• Codice UNSPSC: 12352200
• NACRES: NA.77

Proprietà

• Nome del prodotto: PERK Inhibitor II, GSK2656157,
• Saggio: ≥98% (HPLC)
• Livello qualitativo: 100
• Stato: powder
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: white
• Solubilità: DMSO: 100 mg/mL
• Temperatura di conservazione: −20°C
• Stringa SMILE: Fc1c2c(ccc1c4c5c([n](c4)C)ncnc5N)N(CC2)C(=O)Cc3nc(ccc3)C
• InChI: PRWSIEBRGXYXAJ-UHFFFAOYSA-N

Descrizione

Descrizione generale

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, 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)

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
PERK

Reversible: yes

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Regulatory Review (Z)

Ricostituzione

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.

Altre note

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

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable