heat shock protein inhibitor ii

Heat shock protein (Hsp) inhibitor II is the active form of Hsp inhibitor I and a benzylidene lactam compound that prevents the synthesis of inducible Hsps, such as Hsp105, Hsp72, and Hsp40. Hsp inhibitor II decreases Hsp72 synthesis in vivo and reduces thermotolerance of tumors in SCC VII tumor-containing mice. At 100 μM, it inhibits the development of thermotolerance in COLO 320 DM cells. Inhibition of Hsp70 with Hsp inhibitor II in combination with amphotericin B increases susceptibility of AmB-susceptible (MICs = 0.058 versus 0.27 μg/ml for combined and AmB alone, respectively) and AmB-resistant (MICs = 21.33 versus >32 μg/ml for combined and AmB alone, respectively) strains of A. fumigatus.

VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. It acts on the CTD dimerization interface, preventing the dimerization of HSP90CTD, disrupting the binding of the co-chaperone protein PPID with HSP90CTD, and inhibiting dimerization-dependent functions of HSP90. VWK147 reduces the protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. It induces cell death, including apoptosis (apoptosis), in both cisplatin-sensitive and resistant urothelial carcinoma cells. VWK147 causes LC3-II accumulation, inhibits autophagosome-lysosome fusion to block classical autophagy (autophagy), and triggers non-classical LC3 lipidation independent of the ULK1 and PIK3C3 complex. VWK147 is applicable to research on urothelial carcinoma.