Radicicol (12772-57-5) inhibits heat shock protein 90 (HSP90) activity by binding to the ATP-binding pocket.¹ In cells HSP90 client proteins such as Raf kinase², HIF-1α³ and estrogen receptor⁴ are destabilized and proteolytically degraded. Radicicol inhibits expression of COX-2 without affecting COX-1 expression in LPS-stimulated macrophages (IC₅₀=27 nM).⁵ Inhibits angiogenesis.⁶

References/Citations:

1) Schulte et al. (1999), Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones; Mol. Endocrinol., 13 1435
2) Soga et al. (1998), Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway; J. Biol. Chem., 273 822
3) Hur et al. (2002) Reduction of hypoxia-induced transcription through the repression of hypoxia-inducible factor-1alpha/aryl hydrocarbon receptor nuclear translocator DNA binding by the 90-kDa heat-shock protein inhibitor radicicol; Mol. Pharmacol., 62 975
4) Lee et al. (2002) Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90; Mol. Cell. Endocrinol., 188 47
5) Chanmugam et al. (1995) Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis; J. Biol. Chem., 270 5418
6) Oikawa et al. (1993) Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis; Eur. J. Pharmacol., 241 221