Description 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 (Cat. No. 586005) 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). A cell-permeable pyrrolopyrimidinamine compound that acts as a highly potent inhibitor against EIF2AK3/PERK-catalyzed EIF2α Ser51 phosphorylation in kinase assays (IC50 = 0.4 nM; 30 min preincubation; [ATP] = 5 µM) as well as ER stress-induced PERK autophosphorylation following Thapsigargin (Cat. No. 586005) addition in A549 cultures (by 100% with ≤30 nM inhibitor; 60 min preincubation) by targeting PERK in its inactive conformation at the ATP-binding region. Displays ≥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 exhibits much reduced or little activity against more than 280 other kinases (IC50 >1 µM). Reported to be orally available in dog, mouse, and rat with good pharmacokinetics and retard the growth of established PxBC-3 tumor mass in mice in vivo (by 20% and 59% at the end of a 21 day treatment period with b.i.d. oral dosage of 50 and 150 mg/kg, respectively). The preincubation time-dependent inhibition, extremely slow dissociation rate, as well as the observed PERK selectivity, are all consistent with the inhibitor targeting PERK in its inactive DFG conformation. Packaging 5 mg in Glass bottle 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 Warning Toxicity: Standard Handling (A) Reconstitution Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C. Other Notes Moreno, J.A., et al. 2013. Sci Transl. Med.<\i>5, 1. Axten, J.M., et al. 2012. J. Med. Chem.55, 7193.