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Small Molecule Mediated Protein Degradation - From Art to Science

Authors: Kostic, Milka;

Small Molecule Mediated Protein Degradation - From Art to Science

Abstract

This presentations was given at the the inaugural Proteome-Targeted Drug Discovery Summit 2019 that brought together people interested in pushing the envelop on small-ish molecule based drug discovery and development. From this perspective degrader molecules have really done a lot over the last 5 years to rekindle our imagination of what modalities we can use to go after the undrugged targets. My view point on this emerging field is one of an outsider looking in, and I therefore asked the audience members to share what they think, as well as offered some of my suggestions on how to grow the field further. The most important suggestions I shared are: (1) the importance of developing standards and rules - both related how to validate degrader molecules but also how to share data and enforce the standards - and nucleating a community to carry this work forward; (2) the importance of advocating and promoting the use of small molecule degraders as tools for basic research that is highly complementary to existing research tools; and (3) the importance to cast degraders into a broader perspective as just the first and most visible example of a brand new type of small molecules - one that act as recruiters/inducers of neo-activity.

Keywords

neo-activity, PROTACs, protein CRISPR, SWOT analysis, protein knockdown, small molecules recruiters of neo-activity, targeted protein degradation, degrader molecules

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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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