Can I read Discovery of the GSH responsive “Y-PROTACs” targeting ALK and CDK4/6 as a potential treatment for cancer on EtoBox?

Discovery of the GSH responsive “Y-PROTACs” targeting ALK and CDK4/6 as a potential treatment for cancer by Shirui Wang; Dan Luo; Chunlan Pu; Xinyu Ma; Hongjia Zhang; Zhanzhan Feng; Rui Deng; Su Yu; Yuanyuan Liu; Qing Huang; Rui Li is a Chemistry article available to read on EtoBox.

What is Discovery of the GSH responsive “Y-PROTACs” targeting ALK and CDK4/6 as a potential treatment for cancer about?

Combination of different molecular target inhibitors is an available method to improve the therapeutic effect on tumors. Herein, to achieve both tumor cell targeting and ALK degradation & CDK4/6 inhibition in one molecule, we designed and synthesized a novel GSH responsive “Y-PROTACs”, Y5-3, a highly potent molecule with an IC50 value of 90 nM against H3122 cells, which can be cleaved into ALK PROTAC and CDK4/6 inhibitor moieties in tumor cells. Mechanism studies revealed that Y5-3 exert anti-tumor proliferation activity in vitro not only by ALK degradation and CDK4/6 inhibition, but also by ALK/CDK4 dual degradation. These properties make Y5-3 a GSH responsive multifunctional antitumor agent, and our work provide a new strategy for the development of multifunctional PROTACs.

Who reads Discovery of the GSH responsive “Y-PROTACs” targeting ALK and CDK4/6 as a potential treatment for cancer?

Author

Shirui Wang; Dan Luo; Chunlan Pu; Xinyu Ma; Hongjia Zhang; Zhanzhan Feng; Rui Deng; Su Yu; Yuanyuan Liu; Qing Huang; Rui Li

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Chemistry (Physical Sciences)