[CAS NO. 1337532-29-2] GSK2656157

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PRODUCTS SPECIFICATIONS [1337532-29-2]

Catalog

SLK-S7033

Brand

Selleck

CAS

1337532-29-2

DESCRIPTION [1337532-29-2]

Overview

MDL	MFCD27997885
Molecular Weight	416.45
Molecular Formula	C23H21FN6O
SMILES	NC1=C2C(=CN(C)C2=NC=N1)C=3C(F)=C4C(=CC3)N(C(CC=5N=C(C)C=CC5)=O)CC4

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Description

GSK2656157 is an ATP-competitive and highly selective inhibitor of with of 0.9 nM in a cell-free assay, 500-fold greater against a panel of 300 kinases. GSK2656157 decreases and inhibits excessive .

Features

Orally bioavailable PERK-selective inhibitor that functions independent of eIF2α phosphorylation.

Targets

PERK ^[1]
(Cell-free assay)

0.9 nM

In vitro

Pretreatment of cells with GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2a, ATF4, and CHOP with an IC50 in the range of 10-30 nM. Cells that are exposed to 1 mM GSK2656157 before UPR induction are able to block this effect on protein synthesis. Five of 84 UPR-related genes (DDIT3, HERPUD1, PPP1R15A, C/EBP-beta, and ERN1) are down regulated more than 4-fold by GSK2656157. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC range of 6–25 mM. Thus, GSK2656157 can be used to evaluate the biologic function of PERK in various biologic contexts.

In vivo

Complete inhibition of phospho-PERK Thr980 is observed through 8 hours after a single 50 mg/kg oral dose of GSK2656157. Treatment of mice with 50 or 150 mg/kg twice daily dosing of GSK2656157 results in dose-dependent inhibition of tumor growth in four models; reaching 54–114% tumor growth inhibition at the 150 mg/kg, twice daily dose. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect. Treatment of mice with GSK2656157 results in inhibition of tumor growth in multiple human tumor xenografts.

References

[1] Atkins C, et al. Cancer Res, 2013, 73(6), 1993-2002.

Synonyms

Ethanone, 1-[5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indol-1-yl]-2-(6-methyl-2-pyridinyl)-

1-[5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indol-1-yl]-2-(6-methyl-2-pyridinyl)ethanone

5-[4-Fluoro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

GSK 2656157

PERK inhibitor II

EIF2AK1 inhibitor II

EIF2AK2 inhibitor III

EIF2AK3 inhibitor II

HRI inhibitor II

MEKK2 inhibitor I

PKR inhibitor III

PKR-like ER kinase inhibitor II

1-[5-(4-Amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydroindol-1-yl]-2-(6-methylpyridin-2-yl)ethanone