PROTACs: past, present and future

Li, Ke; Crews, Craig M.

doi:10.1039/d2cs00193d

Cited by 340 publications

(257 citation statements)

References 171 publications

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“…According to the latest statistics in February 2022, PROTACs can induce the degradation of more than 130 target proteins, including cancer, immune disorders, viral infections, neurodegenerative diseases, etc. 18,20–25 As the first protein-degrading drug company, Arvinas recently disclosed the structure and clinical data for the androgen receptor (AR) degrader ARV-110 (NCT03888612) and the estrogen receptor (ERα) degrader ARV-471 (NCT04072952) (Fig. 1C).…”

Section: Introductionmentioning

confidence: 99%

Chemistries of bifunctional PROTAC degraders

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Chemistries of bifunctional PROTAC degraders

et al. 2022

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“…The major concept of PROTAC is to hijack UPS to specifically degrade pathogenic or abnormally overexpressed proteins [ 18 ]. Since firstly proposed in 2001 by Craig M. Crews, this technology has revolutionized the mechanisms of drug-protein interactions in the past two decades [ 16 , 18 , 19 , 20 ]. Most compounds competitively bind with the catalytic site, inhibit kinase phosphorylation, or allosterically decrease the activity of functional proteins [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Small-Molecule PROTACs for Cancer Immunotherapy

Liu¹,

Zhang²,

Xiang³

et al. 2022

Molecules

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Unsatisfactory physicochemical properties of macromolecular drugs seriously hinder their application in tumor immunotherapy. However, these problems can be effectively solved by small-molecule compounds. In the promising field of small-molecule drug development, proteolysis targeting chimera (PROTAC) offers a Cancer Patients. Bosn. J. Basic novel mode of action in the interactions between small molecules and therapeutic targets (mainly proteins). This revolutionary technology has shown considerable impact on several proteins related to tumor survival but is rarely exploited in proteins associated with immuno-oncology up until now. This review attempts to comprehensively summarize the well-studied and less-developed immunological targets available for PROTAC technology, as well as some targets to be explored, aiming to provide more options and opportunities for the development of small-molecule-based tumor immunotherapy. In addition, some novel directions that can magnify and broaden the protein degradation efficiency are mentioned to improve PROTAC design in the future.

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“…The opportunities behind both small molecule-based and antibody-based targeted protein degradation approaches have been curated in other comprehensive reviews in the field. 30–37…”

Section: Recent Advances In Rewriting Protein Degradationmentioning

confidence: 99%