PERK-IN-5

• CAT Number: I043975
• CAS Number: 2616821-91-9
• Molecular Formula: C25H26F2N4O3
• Molecular Weight: 468.50
• Purity: ≥95%
• Synonyms: 2-amino-5-[4-[[(2R)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]amino]-2-ethylphenyl]-N-propan-2-ylpyridine-3-carboxamide
• InChI: InChI=1S/C25H26F2N4O3/c1-4-14-9-19(31-25(34)22(32)15-7-17(26)11-18(27)8-15)5-6-20(14)16-10-21(23(28)29-12-16)24(33)30-13(2)3/h5-13,22,32H,4H2,1-3H3,(H2,28,29)(H,30,33)(H,31,34)/t22-/m1/s1
• InChIKey: YNDQMKBAYRFBMW-JOCHJYFZSA-N
• SMILES: CCC1=C(C=CC(=C1)NC(=O)C(C2=CC(=CC(=C2)F)F)O)C3=CC(=C(N=C3)N)C(=O)NC(C)C

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].
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].

Reference

[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.
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