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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Apoptosis / drug effects*
-
Autoantigens / genetics
-
Autoantigens / metabolism
-
Boronic Acids / chemical synthesis
-
Boronic Acids / chemistry
-
Boronic Acids / pharmacology*
-
Bortezomib
-
Carcinoma, Hepatocellular / genetics
-
Carcinoma, Hepatocellular / metabolism*
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Cell Survival / drug effects
-
Gene Knockdown Techniques
-
Humans
-
Inhibitory Concentration 50
-
Intracellular Signaling Peptides and Proteins
-
Liver Neoplasms / genetics
-
Liver Neoplasms / metabolism*
-
Membrane Proteins / antagonists & inhibitors*
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism
-
Molecular Structure
-
Pyrazines / chemical synthesis
-
Pyrazines / chemistry
-
Pyrazines / pharmacology*
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
Autoantigens
-
Boronic Acids
-
CIP2A protein, human
-
Intracellular Signaling Peptides and Proteins
-
Membrane Proteins
-
Pyrazines
-
Bortezomib