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Targeted protein degradation in cancers: Orthodox PROTACs and beyond

Jin Li1, Xinxin Chen1, Aiping Lu2,3

  • 1Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.

Innovation (Cambridge (Mass.))
|April 10, 2023
PubMed

Insights

Targeted protein degradation (TPD) offers a novel approach to drug discovery by degrading disease-causing proteins. This review explores proteolysis-targeting chimeras (PROTACs) and other TPD strategies for treating various diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Traditional small-molecule inhibitors face limitations in targeting specific proteins.
  • Targeted protein degradation (TPD) presents a promising alternative strategy.
  • Proteolysis-targeting chimeras (PROTACs) leverage the ubiquitin-proteasome system to degrade target proteins.

Purpose of the Study:

  • To review the mechanisms, features, and molecular targets of PROTACs.
  • To summarize PROTAC drugs in clinical trials for cancer therapy.
  • To discuss PROTAC derivatives and alternative TPD strategies.

Main Methods:

  • Review of existing literature on PROTAC technology and TPD strategies.
  • Analysis of PROTAC mechanisms and molecular targets.
  • Summary of clinical trial data for PROTAC-based cancer therapeutics.

Main Results:

  • TPD, particularly PROTACs, has evolved from theoretical concepts to clinical applications.
  • PROTACs are being investigated as cancer therapeutics in clinical trials.
  • Other TPD strategies like LYTACs, ATACs, and molecular glues are also emerging.

Conclusions:

  • TPD strategies, including PROTACs, demonstrate significant potential in the biomedical industry.
  • These approaches offer new avenues for treating oncological, immunological, and other diseases.
  • Continued exploration of TPD holds promise for overcoming drug resistance and targeting previously undruggable proteins.

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