Cell lines

3T3-L1 preadipocytes

Preparation method

The solubility of this compound in ethanol is 25 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

2.5, 5, and 10 μM

Applications

In 3T3-L1 preadipocytes, radicicol dose-dependently reduced intracellular lipids, resulting in significantly lower lipid contents. Radicicol significantly decreased the protein expression of PPARγand C/EBPα protein, which then affected adipocyte differentiation.

Animal models

Male C57BL/6 mice

Dosage form

60 mg/kg; diluted in vehicle (PBS)

Application

In male C57BL/6 mice, radicicol (60 mg/kg) reduced cecal ligation and puncture (CLP)-induced leukocyte rolling by 15% and adhesion by 22%. In these septic mice, radicicol decreased CLP-induced MPO levels in the colon by 24%. Pretreatment with radicicol decreased CLP-evoked formation of MIP-2 and KC down to 68.4 ± 10.5 ng/g and 96.7 ± 15.2 ng/g, respectively, in the colon.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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].

References:
[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.