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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

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The application of PROTAC in HDAC.

Shaoting Chen¹, Yuxiang Zheng¹, Benji Liang¹

¹State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China.

European Journal of Medicinal Chemistry

|August 22, 2023

Summary

Proteolysis targeting chimera (PROTAC) technology enables targeted protein degradation, with Histone deacetylase (HDAC)-PROTACs showing promise. These molecules offer advantages over traditional inhibitors, including enhanced selectivity and overcoming drug resistance.

Keywords:

Histone deacetylases PROTAC Protein degradation Proteolysis-targeting chimera Sirtuins

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Area of Science:

Biochemistry
Molecular Biology
Drug Discovery

Background:

Proteolysis targeting chimera (PROTAC) technology facilitates targeted protein degradation.
Histone deacetylase (HDAC)-PROTACs have emerged as a significant advancement since 2017.
Ten HDACs (HDACs 1-8, HDAC10, and SIRT2) are currently degradable via HDAC-PROTACs.

Purpose of the Study:

To review the development and applications of HDAC-PROTACs.
To highlight the advantages of HDAC-PROTACs over conventional HDAC inhibitors.
To discuss challenges and future directions in HDAC-PROTAC research.

Main Methods:

Literature review of HDAC-PROTAC research.
Analysis of reported HDAC-PROTAC designs and their efficacy.
Comparison of HDAC-PROTACs with traditional HDAC inhibitors.

Main Results:

HDAC-PROTACs have successfully targeted ten different HDACs.
HDAC-PROTACs demonstrate superior selectivity and antiproliferative activity.
They can overcome drug resistance and target enzyme-independent functions.

Conclusions:

HDAC-PROTACs represent a powerful tool for scientific research and therapeutic development.
Rational design of HDAC-PROTACs is crucial for optimizing efficiency and selectivity.
Future clinical applications are anticipated with further in vivo and pharmacological data.