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Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition

1
Department of Chemistry, National Central University, Taoyuan 32001, Taiwan
2
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan
3
Department of Medical Research, National Taiwan University Hospital, Taipei 10048, Taiwan
4
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; https://doi.org/10.3390/molecules181215398
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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