Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-X

Xuan Zhang, Peiyi Zhang, Guangrong Zheng, Dinesh Thummuri, Yonghan He, Xingui Liu, Daohong Zhou

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)14765-14768
Number of pages4
JournalChemical Communications
Volume55
Issue number98
DOIs
StatePublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Electronic, Optical and Magnetic Materials
  • Ceramics and Composites
  • Chemistry(all)
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Materials Chemistry

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