PERK-IN-5

PERK-IN-5 is a highly potent, selectively and orally bioavailable PERK inhibitor (IC50s of 2 and 9 nM for PERK and p-eIF2α, respectively). PERK-IN-5 can significantly inhibit tumor growth in the 786-O renal cell carcinoma xenograft tumor model[1].

Research Areas >> Cancer

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

IC50: 2 nM (PERK), 9 nM (p-eIF2α)[1]

PERK-IN-5 (compound 28) (10-48 µM) is relatively stable in both human and dog hepatocytes and is characterized with long half-lives[1].

PERK-IN-5 (3-100 mg/kg; p.o.; 0.25-24 hours) has robust pharmacokinetics in CD1 mice, with Cmax of 3353 ng/mL, AUC0-last of 5153 h*ng/mL, and bioavailability of 70%[1]. PERK-IN-5 (3 or 10 mg/kg; p.o.; twice daily, for 28 days) has statistically significant tumor growth inhibition[1]. Animal Model: Female CD1 mice[1] (Pharmacokinetics) Dosage: 3, 10, 30 and 100 mg/kg Administration: p.o.; 0.25-24 hours Result: Showed robust pharmacokinetics with Cmax of 3353 ng/mL, AUC0-last of 5153 h*ng/mL, and bioavailability of 70%. Animal Model: BALB/c nude female mice (inoculated subcutaneously with 786-O tumor cells)[1] Dosage: 3 or 10 mg/kg Administration: p.o.; twice daily, for 28 days Result: Showed statistically significant tumor growth inhibition.

[1]. Calvo V, et al. Discovery of 2-amino-3-amido-5-aryl-pyridines as highly potent, orally bioavailable, and efficacious PERK kinase inhibitors. Bioorg Med Chem Lett. 2021;43:128058.