Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity.

Dipti Kanabar, Pamela Farrales, Abbas Kabir, Daniel Juang, Manu Gnanmony, Joseph Almasri, Nicolas Torrents, Snehal Shukla, Vivek Gupta, Vikas V Dukhande, Amber D'Souza, Aaron Muth

Bioorganic & medicinal chemistry letters 2020 Sep 01

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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. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Dipti Kanabar, Pamela Farrales, Abbas Kabir, Daniel Juang, Manu Gnanmony, Joseph Almasri, Nicolas Torrents, Snehal Shukla, Vivek Gupta, Vikas V Dukhande, Amber D'Souza, Aaron Muth. Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity. Bioorganic & medicinal chemistry letters. 2020 Sep 01;30(17):127372