AMG PERK 44

AMG PERK 44 is an orally active and highly selective PERK inhibitor with an IC50 of 6 nM. AMG PERK 44 has 1000-fold and 160-fold selectivity over GCN2 (IC50=7300 nM) and B-Raf (IC50 >1000 nM), respectively[1][2].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> PERK

IC50: 6 nM (PERK)[1]

AMG PERK 44 has an IC50 of 84 nM for cell pPERK[1].

AMG PERK 44 (orally; 3-100 mg/kg) robustly inhibits PERK autophosphorylation in this assay (ED50=3 mg/kg; ED90=60 mg/kg at the 4 hours time point), and >50% target coverage is maintained for 24 h in a time course PD assay when dosed at 100 mg/kg po[1]. AMG PERK 44 (iv; 1 mg/kg) has a CL of 1.6 L/h•kg, a Vss of 3.6 L/kg and MRT of 2.3 hours in Sprague-Dawley rats and male CD-1 mice[1]. Animal Model: Four- to six-week old naive athymic nude mice[1] Dosage: 3, 10, 30, 100 mg/kg Administration: Orally Result: Robustly inhibited PERK autophosphorylation in this assay (ED50=3 mg/kg; ED90=60 mg/kg at the 4 hours time point). Animal Model: Sprague-Dawley rats and male CD-1 mice[1] Dosage: 1 mg/kg (Pharmacokinetic Analysis) Administration: Iv Result: Had a CL of 1.6 L/h•kg, a Vss of 3.6 L/kg and a MRT of 2.3 hours.

[1]. Smith AL, et al. Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK). J Med Chem. 2015 Feb 12;58(3):1426-41.

[2]. Roest G, et al. The ER Stress Inducer l-Azetidine-2-Carboxylic Acid Elevates the Levels of Phospho-eIF2α and of LC3-II in a Ca2+-Dependent Manner. Cells. 2018 Nov 30;7(12). pii: E239.