GSK-2656157

• CAT Number: I001285
• CAS Number: 1337532-29-2
• Molecular Formula: C23H21FN6O
• Molecular Weight: 416.46
• Purity: ≥95%
• Target: PERK
• Solubility: DMSO: ≥ 41 mg/mL
• Storage: Store at -20 C
• IC50: 0.9 nM [1]
• IUPAC Name: 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
• InChI: InChI=1S/C23H21FN6O/c1-13-4-3-5-14(28-13)10-19(31)30-9-8-16-18(30)7-6-15(21(16)24)17-11-29(2)23-20(17)22(25)26-12-27-23/h3-7,11-12H,8-10H2,1-2H3,(H2,25,26,27)
• InChIKey: PRWSIEBRGXYXAJ-UHFFFAOYSA-N
• SMILES: CC1=NC(=CC=C1)CC(=O)N2CCC3=C2C=CC(=C3F)C4=CN(C5=C4C(=NC=N5)N)C

GSK2656157 (CAT: I001285) is an ATP-competitive inhibitor that specifically targets the enzyme activity of PERK (protein kinase RNA-like endoplasmic reticulum kinase). It displays a potent inhibitory effect on PERK with an IC50 of 0.9 nM. Importantly, GSK2656157 exhibits high selectivity for PERK, as it has IC50 values greater than 100 nM when tested against a panel of 300 kinases. This selectivity profile suggests that GSK2656157 has minimal off-target effects on other kinases. The inhibition of PERK by GSK2656157 provides a valuable tool for studying PERK-mediated cellular processes and has potential therapeutic applications in diseases associated with PERK dysregulation, such as cancer and neurodegenerative disorders.

Reference

1:When PERK inhibitors turn out to be new potent RIPK1 inhibitors: critical issues on the specificity and use of GSK2606414 and GSK2656157. Rojas-Rivera D, Delvaeye T, Roelandt R, Nerinckx W, Augustyns K, Vandenabeele P, Bertrand MJM.Cell Death Differ. 2017 Apr 28. doi: 10.1038/cdd.2017.58. [Epub ahead of print] PMID: 28452996
2:GSK2656157, a PERK inhibitor, reduced LPS-induced IL-1β production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells. Ando T, Komatsu T, Naiki Y, Takahashi K, Yokochi T, Watanabe D, Koide N.Immunopharmacol Immunotoxicol. 2016 Aug;38(4):298-302. doi: 10.1080/08923973.2016.1192191. Epub 2016 Jun 16. PMID: 27251848
3:Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development. Axten JM, Romeril SP, Shu A, Ralph J, Medina JR, Feng Y, Li WH, Grant SW, Heerding DA, Minthorn E, Mencken T, Gaul N, Goetz A, Stanley T, Hassell AM, Gampe RT, Atkins C, Kumar R.ACS Med Chem Lett. 2013 Aug 12;4(10):964-8. doi: 10.1021/ml400228e. eCollection 2013 Oct 10. PMID: 24900593 Free PMC Article
4:Evidence for eIF2α phosphorylation-independent effects of GSK2656157, a novel catalytic inhibitor of PERK with clinical implications. Krishnamoorthy J, Rajesh K, Mirzajani F, Kesoglidou P, Papadakis AI, Koromilas AE.Cell Cycle. 2014;13(5):801-6. doi: 10.4161/cc.27726. Epub 2014 Jan 8. PMID: 24401334 Free PMC Article