Radicicol is a macrocyclic antifungal antibiotic that inhibits protein tyrosine kinase. Isolated from Monocillium nordinii, it binds to and inhibits Hsp90 at very low concentrations (20nM). Heat shock Protein 90(Hsp90), is a molecular chaperone that mediates the folding of ?a number of oncogenic proteins, it is an attractive target for inhibiton by anticancer agents.
Radicicol binds to a highly conserved pocket in the Hsp90 protein and inhibits the intrinsic ATPase activity of Hsp90.?Radicicol induces the differentiation of HL-60 cells into macrophages, blocking cell cycle at G1 and G2. It suppresses NIH 3T3 cell transformation by diverse oncogenes such as?src,?ras?and?mos?and also suppresses the expression of mitogen-inducible cyclooxygenase-2. As a cell differentiation modulator, radicicol has anti-angiogenic activity?in vivo, inhibiting the proliferation of and plasminogen activator production by vascular endothelial cells.
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