GSK2656157

GSK2656157 is a **small molecule inhibitor** developed as a highly selective, ATP-competitive inhibitor of **protein kinase R-like endoplasmic reticulum kinase (PERK/eIF2AK3)**, a key enzyme in the unfolded protein response (UPR) pathway[1][2][3][6][7]. It exhibits **nanomolar potency** (IC50 ≈ 0.9 nM for PERK) and displays high specificity relative to other kinases[1][2][7]. In preclinical cancer models, GSK2656157 inhibits ER stress-induced PERK and eIF2α phosphorylation as well as downstream effectors such as ATF4 and CHOP, resulting in tumor growth inhibition and reversible pancreatic toxicity[1][3][7]. Notably, this compound can also activate the integrated stress response (ISR) via GCN2 at higher concentrations and directly inhibits RIPK1 kinase at micromolar concentrations, independently of PERK[2][5]. It was initially developed by GSK (GlaxoSmithKline) as an optimized PERK inhibitor for oncology and other indications but remains investigational[6][7].

Other names

GSK-2656157GSK2656157GSK 2656157