PERK Inhibitor I, GSK2606414 – CAS 1337531-89-1 – Calbiochem

Descrição detalhada : 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 EIF2alpha 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.
Sinónimos : PERK Inhibitor I, GSK2606414 - CAS 1337531-89-1 - Calbiochem; MERTK Inhibitor II, RP38 Inhibitor II, TAM Family RTK Inhibitor II, Double-stranded RNA-activated Protein Kinase Inhibitor II, Double-stranded RNA-dependent Protein Kinase Inhibitor II, EIF2AK3 Inhibitor I, PKR Inhibitor II, 7-Methyl-5-(1-((3-trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine, 1-(5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)indolin-1-yl)-2-(3-(trifluoromethyl)phenyl)ethanone, DDR2 Inhibitor I, EIF2AK1 Inhibitor I, EIF2AK2 Inhibitor II, HRI Inhibitor I, MLCK Inhibitor VI, MLK2/MAP3K10 Inhibitor I, PKR-like ER Kinase Inhibitor I, Aurora Kinase Inhibitor IX, BRK Inhibitor I, c-Kit Inhibitor III, Mer RTK Inhibitor II
Fórmula molecula r: C24H20F3N5O
Armazenamento : -20C
Embalagem : 1X5MG