MilliporeSigma™ Calbiochem™ InSolution™ PERK Inhibitor I, GSK2606414

Description

• A cell-permeable pyrrolopyrimidinamine compound that acts as a highly potent inhibitor against EIF2AK3/PERK-catalyzed EIF2α Ser51 phosphorylation in kinase assays (IC 50 = 0.4nM; 30 min preincubation; [ATP] = 5μM) as well as ER stress-induced PERK autophosphorylation following Thapsigargin (Cat
• No
• 586005) addition in A549 cultures (by 100% with ≤30nM 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 (IC 50 = 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 (IC 50 >1μM)
• 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 150mg/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.