Conglobatin

Conglobatin is a dimeric macrolide dilactone originally isolated from S. conglobatus. It disrupts binding of heat shock protein 90 (Hsp90) to the co-chaperone Cdc37 complex and induces downregulation of client protein expression in SK-BR-3 breast cancer cells. It also inhibits cell proliferation in HER2+ breast cancer cell lines (IC50s = 12.9-61.5 uM, respectively) and decreases the number of invasive cells in vitro. When combined with lapatinib , tumor growth of SK-BR-3 mouse xenografts was reduced to a greater degree than with conglobatin alone. Conglobatin has various anticancer effects in esophageal squamous cell carcinoma (ESCC) models as well, including an inhibition of cell proliferation in KYSE510 cells (IC50 = 9.31 uM). It also inhibits β1 integrin activation leading to a loss of cellular adhesion.