Gankyrin is an oncoprotein directly involved in multiple protein-protein interactions (PPIs) in which modulate the cell cycle, cell growth, and cell proliferation. Gankyrin overexpression in a variety of cancers has been associated with abnormal cellular events, such as enhanced proliferation and metastasis. One of the key PPIs of gankyrin which regulates cancer cell proliferation and metastasis is that with the 26S proteasome. This interaction regulates degradation of key tumor suppressor proteins which in turn regulates cell proliferation. Recently.The first small molecule inhibitor of gankyrin, cjoc42, was discovered, which inhibits the gankyrin-26S proteasome interaction leading to diminished proliferation in certain cancers. Despite this advance, cjoc42 has 2 major flaws: low binding affinity and poor water solubility In order to improve on the cjoc42 scaffold and address these issues, a series of heterocycles were introduced to the cjoc42 scaffold. Herein we describe the synthesis and biological evaluation of these next-generation cjoc42-based gankyrin inhibitors.

Efforts to improve the cjoc42 scaffold for binding gankyrin and enhanced water solubility

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.