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Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition

Department of Chemistry, National Central University, Taoyuan 32001, Taiwan
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan
Department of Medical Research, National Taiwan University Hospital, Taipei 10048, Taiwan
National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei 10002, Taiwan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2013, 18(12), 15398-15411;
Received: 25 August 2013 / Revised: 20 November 2013 / Accepted: 28 November 2013 / Published: 11 December 2013
CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure–activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors. View Full-Text
Keywords: CIP2A; bortezomib; apoptosis CIP2A; bortezomib; apoptosis
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Hou, D.-R.; Huang, A.-C.; Shiau, C.-W.; Wang, C.-Y.; Yu, H.-C.; Chen, K.-F. Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition. Molecules 2013, 18, 15398-15411.

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