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Updated: Jan 16, 2026

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

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Published on: January 12, 2024

Proteolysis-Targeting Chimera (PROTAC): Current Applications and Future Directions.

Gang Fan^1,2, Shilin Chen^3,2, Qingping Zhang^4,2

¹Medical Research Center Affiliated Nanshan Hospital of Shenzhen University Shenzhen China.

|October 6, 2025

Summary

This summary is machine-generated.

Targeted protein degradation (TPD) revolutionizes drug discovery by actively removing disease proteins. Proteolysis-targeting chimeras (PROTACs) show significant clinical progress for challenging targets and complex diseases.

Keywords:

PROTAC clinical translation drug discovery target protein degradation ubiquitin–proteasome system

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Area of Science:

Drug Discovery and Development
Molecular Biology
Oncology

Background:

Targeted protein degradation (TPD) offers a novel therapeutic strategy by actively eliminating disease-driving proteins, unlike traditional inhibition.
This approach expands treatment options for previously undruggable targets, including transcription factors (MYC, STAT3) and mutant oncoproteins (KRAS G12C).
Proteolysis-targeting chimeras (PROTACs) are the leading TPD platform, with clinical trials demonstrating significant progression.

Purpose of the Study:

To comprehensively review PROTAC development across various therapeutic areas.
To analyze key targets and evaluate the clinical progression of breakthrough PROTAC candidates.
To discuss challenges and future directions in PROTAC technology for complex diseases.

Main Methods:

Review of existing literature on PROTAC development and clinical trials.
Analysis of PROTAC applications targeting kinases, hormone receptors, antiapoptotic proteins, and epigenetic modulators.
Evaluation of clinical data for candidates like ARV-110, ARV-471, and BTK degraders.

Main Results:

PROTACs are advancing clinically for targets like MYC, STAT3, KRAS G12C, and BTK.
Successful clinical progression is noted for prostate cancer (ARV-110) and breast cancer (ARV-471) PROTACs.
Key challenges such as the 'hook effect' and oral bioavailability limitations are identified.

Conclusions:

PROTAC technology represents a paradigm shift in drug discovery, enabling the targeting of previously intractable proteins.
Continued innovation in delivery strategies, tissue-specific design, and E3 ligase expansion is crucial for overcoming challenges.
PROTACs hold significant potential for transforming the treatment of complex diseases resistant to conventional therapies.