HC-5404

HC-5404 is an inhibitor of protein kinase R-like ER kinase (PERK, IC50 = 4 nM in a cell-free assay). It is selective for PERK over a panel of 25 kinases at 1 mM. HC-5404 reduces the levels of phosphorylated eukaryotic translation initiation factor 2alpha subunit (eIF2alpha) in HEK293 cells (IC50 = 33 nM). It reduces tumor volume in a 786-O renal cell carcinoma mouse xenograft model when administered at a dose of 30 mg/kg once or twice per day. HC-5404 has an additive effect on tumor growth inhibition when administered in combination with axitinib (Cay13813), cabozantinib (XL184, Item No. 18464), lenvatinib (Cay19375), or sunitinib (Cay13159) in a 786-O mouse xenograft model.. SMILES: O=C(NC1=CC(C)=C(C2=CN=C(C(C(NC(C)C)=O)=C2)N)C=C1)[C@H](O)C3=CC(F)=CC(F)=C3. InChi Code: InChI=1S/C24H24F2N4O3/c1-12(2)29-23(32)20-9-15(11-28-22(20)27)19-5-4-18(6-13(19)3)30-24(33)21(31)14-7-16(25)10-17(26)8-14/h4-12,21,31H,1-3H3,(H2,27,28)(H,29,32)(H,30,33)/t21-/m1/s1. InChi Key: BRIWRAFDHZTJPE-OAQYLSRUSA-N