516535
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.
Synonym(s):
PERK Inhibitor I, GSK2606414
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All Photos(2)
About This Item
Empirical Formula (Hill Notation):
C24H20F3N5O
CAS Number:
Molecular Weight:
451.44
MDL number:
UNSPSC Code:
12352200
Recommended Products
Quality Level
Assay
≥99% (HPLC)
form
powder
manufacturer/tradename
Calbiochem®
storage condition
OK to freeze
protect from light
color
white
solubility
DMSO: 100 mg/mL
shipped in
ambient
storage temp.
−20°C
SMILES string
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)
InChI key
PXVQGBJMIQCDEX-UHFFFAOYSA-N
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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.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
Perk
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.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Storage Class Code
11 - Combustible Solids
WGK
WGK 3
Flash Point(F)
Not applicable
Flash Point(C)
Not applicable
Certificates of Analysis (COA)
Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.
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