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 (AmB; ) 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.
