title: Bortezomib congeners induce apoptosis of hepatocellular carcinoma via CIP2A inhibition.
abstract: 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.
authors: Duen-Ren
authors: DR
authors: Hou
authors: Ann-Chi
authors: AC
authors: Huang
authors: Chung-Wai
authors: CW
authors: Shiau
authors: Chun-Yi
authors: CY
authors: Wang
authors: Hui-Chuan
authors: HC
authors: Yu
authors: Department of Chemistry, National Central University, Taoyuan 32001, Taiwan. kfchen1970@ntu.edu.tw.
authors: Kuen-Feng
authors: KF
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000069286:Bortezomib; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001324:Autoantigens; D001897:Boronic Acids; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011719:Pyrazines; D000069286:Bortezomib