Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL. Issue 98 (22nd November 2019)

• Record Type: Journal Article
• Authors: Zhang, Xuan; Thummuri, Dinesh; He, Yonghan; Liu, Xingui; Zhang, Peiyi; Zhou, Daohong; Zheng, Guangrong
• Is Part Of: Chemical communications. Volume 55:Issue 98(2019)
• Page Start: 14765
• Page End: 14768
• Publication Date: 2019-11-22
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c9cc07217a
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : A proof-of-concept study demonstrates the potential of utilizing a PROTAC approach to achieve tissue selectivity. Abstract : BCL-XL, an anti-apoptotic BCL-2 family protein, plays a key role in cancer cell survival. However, the potential of BCL-XL as an anti-cancer target has been hampered by the on-target platelet toxicity because platelets depend on BCL-XL to maintain their viability. Here we report the development of a PROTAC BCL-XL degrader, XZ424, which has increased selectivity for BCL-XL -dependent MOLT-4 cells over human platelets compared with conventional BCL-XL inhibitors. This proof-of-concept study demonstrates the potential of utilizing a PROTAC approach to achieve tissue selectivity.