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.

Gankyrin是一种在多种癌症类型中过表达的癌蛋白，似乎在调节细胞增殖，细胞生长和细胞迁移中起关键作用。这些作用主要是由于gankyrin与26S蛋白酶体的蛋白质相互作用。我们先前发表了一项研究cjoc42的芳基磺酸酯的研究，目的是增强gankyrin的结合并抑制癌细胞的增殖。为了进一步提高cjoc42支架的gankyrin结合能力，开发了针对cjoc42的芳基-三唑部分的广泛SAR。我们的cjoc42衍生物表现出增强的gankyrin结合，以及增强的针对Hep3B，HepG2，A549和MDA-MB-231癌细胞系的抗增殖活性。