Discovery of 5,6-Bis(4-methoxy-3-methylphenyl)pyridin-2-amine as a WSB1 Degrader to Inhibit Cancer Cell Metastasis.

By J. Che, Zegao Jin, Fangjie Yan, Jieqiong You, Jiangfeng Xie, Binhui Chen, Gang Cheng, Hong Zhu, Qiaojun He, Yongzhou Hu and 3 more. 2021

11 citations recorded by the source corpus.

The gain of cell motility is an essential prerequisite for cancer metastasis. The ubiquitin ligase subunit WD repeat and SOCS box-containing 1 (WSB1) has been demonstrated to regulate hypoxia-driven tumor cell migration. However, there is still a lack of methods for discovering inhibitors targeting the WSB1 axis. Here, we employed phenotypic screening models and identified compound 4 that displayed migration inhibitory activity against WSB1-overexpressing cells. Further studies indicated that it may function as a WSB1 degrader, thus leading to the accumulation of the Rho guanosine diphosphate dissociation inhibitor 2 (RhoGDI2) protein, reversing the expression of downstream F-actin and formation of membrane ruffles, and disturbing the migration capacity of cancer cells. Moreover, compound 4 exhibited a promising in vivo anticancer metastatic effects. Our findings show the discovery of a new WSB1 degrader, providing a unique solution for the treatment of cancer metastasis.

Subfields: Cancer Research, Molecular Biology, Oncology

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In Molecular Biology

1. Yi Zhao
2. Zhenyu Yang
3. Runsheng Chen
4. Xiaoxi Zeng

Citations in the corpus

• AlphaFold2 and its applications in the fields of biology and medicine (2023, background): “Weng et al. 92 applied AF2 to predict the 3D structure of WSB1 (SOCS-box-containing WD-40 protein), a new potential anticancer target 93 – 95 with 3D structural information not available.”