Gankyrin is an ankyrin-repeat oncoprotein involved in various biological processes, such as cell proliferation, apoptosis, invasion and metastasis. Gankrin has been found to be overexpressed in numerous cancer types, such as esophageal squamous cell carcinoma, hepatocellular carcinoma, breast, ovarian, glioblastoma, colorectal, pancreatic and lung cancer. Through its involvement in several protein-protein interactions (PPIs), gankyrin regulates several oncogenic pathways. This demonstrates gankyrin’s potential as a therapeutic target for treating certain cancers. Specifically, inhibiting specific gankyrin PPIs has been suggested as a viable therapeutic strategy. Currently, there is only one small molecule (cjoc42) that binds gankyrin while simultaneously inhibiting its interaction with the 26S proteasome. This inhibition, has been shown to normalize cell growth and inhibit cancer cell proliferation. In order for cjoc42 to properly bind gankyrin, it has been previously suggested that it adopts a U-shaped structure. In order to further improve gankyrin binding affinity, we synthesized a series of conformationally flexible as well as constrained compounds and evaluated them for their gankyrin binding ability. Herein, we report the synthesis and evaluation of these derivatives for binding gankyrin.

Development of conformationally constrained cjoc42 derivatives for binding gankyrin

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.