Radicicol

An Anticancer Antibiotic. An antifungal macrocyclic antibiotic, originally recognized as a protein tyrosine kinase inhibitor. Radicicol inhibits p60v-src kinase activity, and tyrosine phosphorylation of p53/56lyn.
The specific inhibition of the chaperone Hsp90 confers anticancer properties to Radicicol. In eukaryotic cells, Hsp90 catalyzes the final activation step of many regulatory proteins. Cells that lose Hsp90 function are severely compromised and cannot progress through the cell cycle.
Radicicol, similarly to Geldanamycin, binds to the nucleotide-binding pocket, and inhibits ATPase activity of Hsp90. This causes destabilization of Hsp90 client proteins (v-Src, Raf-1, ErbB2 Ras), many of which are essential for tumor cell growth. Oncogene induced transformation of NIH 3T3 cells (src, ras, and mos) is suppressed by radicicol and it also disrupts the K-Ras-activated signaling pathways by selective depletion of Raf kinase. In addition, it also exhibits anti-angiogenic activity in vivo, and reduces the expression of VEGF.
Radicicol inhibits AP-1-, NF-kB- and serum response factor (SRF)-mediated transcription. It inhibits the expression of COX-2 without affecting COX-1 expression in LPS-stimulated macrophages, and induces the differentiation of HL-60 cells into macrophages, by blocking the cell cycle at G1 and G2 sites. Cell Signaling Activators and Inhibitors; Anticancer Compounds.
Protein Kinase Inhibitors and Activators; SRC inhibitor.

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