Molecular glue degrader for tumor treatment

Front Oncol. 2024 Dec 12:14:1512666. doi: 10.3389/fonc.2024.1512666. eCollection 2024.

Abstract

Targeted Protein Degradation (TPD) represented by Proteolysis-Targeting Chimeras (PROTAC) is the frontier field in the research and development of antitumor therapy, in which oral drug HP518 Receives FDA Proceed Authorization for its IND Application for Prostate Cancer Treatment. Recently, molecular glue, functioning via degradation of the target protein is emerging as a promising modality for the development of therapeutic agents, while exhibits greater advantages over PROTAC, including improved efficiency, resistance-free properties, and the capacity to selectively target "undruggable" proteins. This marks a revolutionary advancement in the landscape of small molecule drugs. Given that molecular glue research is still in its early stage, we summarized the mechanisms of molecular glue, the promising drugs in clinical trials and diverse feasible design strategies for molecular glue therapeutics.

Keywords: clinical trials; design strategies; mechanism; molecular glue degrader; tumor.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Zhongyuan Young Top Talent Project (ZYCYU202012163). This funding agency provided financial support for the experimental design, data collection, and analysis of results. The agency played no role in the interpretation of data or the preparation of the manuscript. This study was also funded by the Henan Medical Science and Technology Tackling Program Key Project (SBGJ202302026); funded by QL. This grant supported the computational analysis and modeling portion of the research, including the development of software tools used in the study. The agency had no involvement in the manuscript writing or decision-making processes.