VER-50589

The heat shock proteins (Hsps) act as molecular chaperones. Hsp90 is an abundant protein with roles in protein folding, cell signaling, and cancer. VER-50589 is an isoxazole compound that inhibits Hsp90 with an IC50 value of 21 nM. It produces a mean cellular antiproliferative GI50 value of 78 nM when tested against a human cancer cell line panel. Consistent with inhibition of Hsp90, VER-50589 induces the expression of Hsp27 and Hsp72 while reducing the client proteins C-RAF, B-RAF, survivin, and PRMT5, causing cell cycle arrest and apoptosis. VER-50589 shows favorable pharmacokinetics and impairs tumor growth in animals. Importantly, glioblastoma cells do not acquire resistance to VER-50589 and resistance to other Hsp90 inhibitors does not produce cross-resistance to VER-50589.Formal Name: 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-3-isoxazolecarboxamide. CAS Number: 747413-08-7. Molecular Formula: C19H17ClN2O5. Formula Weight: 388.8. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. SMILES: CCNC(=O)c1noc(c1c1ccc(OC)cc1)c1cc(Cl)c(O)cc1O. InChi Code: InChI=1S/C19H17ClN2O5/c1-3-21-19(25)17-16(10-4-6-11(26-2)7-5-10)18(27-22-17)12-8-13(20)15(24)9-14(12)23/h4-9,23-24H,3H2,1-2H3,(H,21,25). InChi Key: JXPCDMPJCKNLBY-UHFFFAOYSA-N.