516535

GSK2606414

≥99% (HPLC), powder, PERK inhibitor, Calbiochem^®

• Synonyme(s) : PERK Inhibitor I, GSK2606414
• Formule empirique (notation de Hill): C₂₄H₂₀F₃N₅O
• Numéro CAS: 1337531-89-1
• Poids moléculaire : 451.44
• Numéro MDL: MFCD25976926
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• product name: PERK Inhibitor I, GSK2606414, GSK2606414 is a cell-permeable, highly potent inhibitor of EIF2AK3/PERK (IC₅₀ = 0.4 nM; [ATP] = 5 µM). Targets PERK in its inactive DFG conformation at the ATP-binding region.
• Niveau de qualité: 200
• Pureté: ≥99% (HPLC)
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: white
• Solubilité: DMSO: 100 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: −20°C
• Chaîne SMILES: O=C(CC1=CC=CC(C(F)(F)F)=C1)N2CCC3=C2C=CC(C4=CN(C)C5=C4C(N)=NC=N5)=C3
• InChI: 1S/C24H19F4N5O/c1-32-11-18(21-22(29)30-12-31-23(21)32)14-2-3-19-15(9-14)4-5-33(19)20(34)8-13-6-16(24(26,27)28)10-17(25)7-13/h2-3,6-7,9-12H,4-5,8H2,1H3,(H2,29,30,31)
• Clé InChI: PXVQGBJMIQCDEX-UHFFFAOYSA-N

Description

Description générale

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.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
Perk

Reversible: yes

Target IC₅₀: 0.4 nM against EIF2AK3/PERK-catalyzed EIF2&alpha

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Autres remarques

2024 CiteAb Award Winner for Supplier Succeeding in Parkinson′s Research

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable