Merck, 516535-5MG, PERK Inhibitor I, GSK2606414

General description
A cell-permeable pyrrolopyrimidamine compound that acts as a highly potent EIF2AK3/PERK inhibitor (IC₅₀ = 0.4 nM; [ATP] = 5 µM) by targeting PERK in its inactive DFG conformation at the ATP-binding region, while displaying ≥385-fold selectivity over c-Kit, Aurora B, BRK, HRI/EIF2AK1, MLK2/MAP3K10, c-MER, DDR2, PKR/EIF2AK2, and MLCK2/MYLK2 (IC₅₀ = 154, 407, 412, 420, 452, 474, 524, 696, and 701 nM, respectively) and little activity against more than 280 other kinases (IC₅₀ >1 µM). Shown to block ER stress-induced PERK autophosphorylation following Thapsigargin addition in A549 cultures in vitro (by 100% at ≤30 nM; 60 min preincubation) and effectively retard PxBC-3 tumor growth in mice in vivo (50 and 150 mg/kg/12 h p.o.). Also available as a 25 mM solution in DMSO (Cat. No. 508340).
Biochem/physiol Actions
Cell permeable: yes
Primary Target
Perk
Reversible: yes
Target IC₅₀: 0.4 nM against EIF2AK3/PERK-catalyzed EIF2&alpha
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Other Notes
2024 CiteAb Award Winner for Supplier Succeeding in Parkinson′s Research
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)