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Overview
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Background
Radicicol is an inhibitor of the ATPase/kinase with IC50 values of ＜1μM, 100μM and 400μM, respectively for Hsp90, Topo VI and PDK3 [1].Radicicol inhibits the activities of Hsp90, Topo VI and PDK3 by blocking ATP binding to them. Radicicol binds to the ATP-binding site in the C-terminal domain of PDK3 and competes with ATP. The inhibition does not cause the structure change of PDK3. Radicicol also shows a weak inhibition of PDK1 and PDK2 with IC50 value of 230mM and Ki value of 23μM, respectively [1].As an inhibitor of Hsp90, radicicol is reported to downregulate the expression of PPARγ, C/EBPα , FAS and FABP4 results in the inhibition of lipid accumulation in 3T3-L1 adipocytes. Radicicol also has effects on cell cycle arrest and the PDK1/Akt pathway, thus causing the inhibition of the differentiation of 3T3-L1 preadipocytes. In addition, it is shown that radicicol increases the activation of the caspase-8- and Bid-dependent pathway and then enhances TRAIL-induced apoptosis in ovarian carcinoma cell lines [2, 3].
[1] Kato M, Li J, Chuang JL, Chuang DT. Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 2007 Aug;15(8):992-1004.
[2] He Y, Li Y, Zhang S, Perry B, Zhao T, Wang Y, Sun C. Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes. Biochem Biophys Res Commun. 2013 Jun 28;436(2):169-74.
[3] Kim YJ, Lee SA, Myung SC, Kim W, Lee CS. Radicicol, an inhibitor of Hsp90, enhances TRAIL-induced apoptosis in human epithelial ovarian carcinoma cells by promoting activation of apoptosis-related proteins. Mol Cell Biochem. 2012 Jan;359(1-2):33-43.
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