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Review
. 2021;2(6):511-521.
doi: 10.37349/etat.2021.00061. Epub 2021 Dec 31.

The clinical advances of proteolysis targeting chimeras in oncology

Hao Xie  1 , Junjia Liu  2 , Diego M Alem Glison  1 , Jason B Fleming  1
Affiliations
Review

The clinical advances of proteolysis targeting chimeras in oncology

Hao Xie et al. Explor Target Antitumor Ther. 2021.

Abstract

Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances. A number of PROTACs have entered a late stage of preclinical development. Several of them are either in phase 1/2 clinical trials or approaching approval for initial clinical evaluation. This article discusses the preclinical and clinical findings of PROTACs of clinically relevant protein targets in cancer.

Keywords: clinical trial; phase 1; proteolysis targeting chimera.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Chemical structures of disclosed PROTAC degraders in clinical development. CRBN: cereblon; Ub: ubiquitin; VHL: von Hippel-Lindau
Figure 2.
Figure 2.
Design of selected clinical trials of PROTAC degraders. PK: pharmacokinetic; PD: pharmacodynamic; RP2D: recommended phase II dose; CDK4/6: cyclin dependent kinase 4/6
See this image and copyright information in PMC

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