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

• Published in: Bioorganic & medicinal chemistry letters Vol. 30; no. 17; p. 127372
• Main Authors: Kanabar, Dipti, Farrales, Pamela, Kabir, Abbas, Juang, Daniel, Gnanmony, Manu, Almasri, Joseph, Torrents, Nicolas, Shukla, Snehal, Gupta, Vivek, Dukhande, Vikas V., D'Souza, Amber, Muth, Aaron
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2020; Elsevier
• Subjects: Antiproliferation; Breast cancer; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Gankyrin; Life Sciences & Biomedicine; Liver cancer; Lung cancer; Pharmacology & Pharmacy; Physical Sciences; Protein-protein interactions; Science & Technology; Antiproliferation; Liver cancer; Breast cancer; Gankyrin; Lung cancer; Protein-protein interactions; PROTEIN; METASTASIS; ONCOPROTEIN GANKYRIN; CHAPERONE; DISCOVERY; BREAST-CANCER; RB; REGULATOR; PATHWAY; DEGRADATION
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2020.127372

[Display omitted] 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.