The PROTACtable genome

Melanie Schneider

doi:10.1038/s41573-021-00245-x

The PROTACtable genome

2021-07-20

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Lykourgos‐Panagiotis Zalmas

Veerabahu Shanmugasundaram

DOI：10.1038/s41573-021-00245-x

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Targeted protein degradation by proteolysis-targeting chimeras (PROTACs) is attracting substantial interest as a therapeutic modality that could circumvent some limitations of traditional small-molecule drugs. This article presents a systematic approach to assessing the PROTAC tractability (PROTACtability) of protein targets, which could support decision-making on whether a particular target may be amenable to modulation using a PROTAC. Proteolysis-targeting chimeras (PROTACs) are an emerging drug modality that may offer new opportunities to circumvent some of the limitations associated with traditional small-molecule therapeutics. By analogy with the concept of the 'druggable genome', the question arises as to which potential drug targets might PROTAC-mediated protein degradation be most applicable. Here, we present a systematic approach to the assessment of the PROTAC tractability (PROTACtability) of protein targets using a series of criteria based on data and information from a diverse range of relevant publicly available resources. Our approach could support decision-making on whether or not a particular target may be amenable to modulation using a PROTAC. Using our approach, we identified 1,067 proteins of the human proteome that have not yet been described in the literature as PROTAC targets that offer potential opportunities for future PROTAC-based efforts.

Keywords:

SELECTIVE DEGRADATION

PROTEIN-DEGRADATION

UBIQUITIN LIGASES

SLC TRANSPORTERS

TARGETS

DISCOVERY

DEGRADER

IDENTIFICATION

COMPLEX

DESIGN

The PROTACtable genome

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