ABSTRACT
Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteasome. We previously published a study exploring the aryl sulfonate ester of cjoc42 in an effort to enhance gankyrin binding and inhibit cancer cell proliferation. In order to further improve the gankyrin binding ability of the cjoc42 scaffold, an extensive SAR for the aryl-triazole moiety of cjoc42 was developed. Our cjoc42 derivatives exhibited enhanced gankyrin binding, as well as enhanced antiproliferative activity against Hep3B, HepG2, A549, and MDA-MB-231 cancer cell lines.
Subject(s)
Antineoplastic Agents/chemistry , Benzenesulfonates/chemistry , Proteasome Endopeptidase Complex/metabolism , Proto-Oncogene Proteins/metabolism , Triazoles/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Benzenesulfonates/metabolism , Benzenesulfonates/pharmacology , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Molecular Dynamics Simulation , Proteasome Endopeptidase Complex/chemistry , Protein Binding , Proto-Oncogene Proteins/chemistry , Structure-Activity Relationship , Triazoles/metabolism , Triazoles/pharmacologyABSTRACT
To treat a patient who needed a replacement for a maxillary obturator prosthesis, a new obturator prosthesis was fabricated from polyetheretherketone (PEEK), a material often used in medicine but seldom in dentistry. This material provided the patient with a better-adjusted, more functional, and lighter prosthesis.