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Observations #11
A set of ideas and observations from a week’s worth of work analyzing businesses and technologies.
Targeted protein degradation
Proteolysis-targeting chimeras (PROTAC) and other targeted protein degradation drugs use the ubiquitin–proteasome system to selectively degrade target proteins. This work was pioneered by Arvinas — https://axial.substack.com/p/axial-arvinas where they just reported the first human data on the use of PROTACs last week, and opens up a whole new field of currently undruggable targets to pursue.
However, less than 10 (I think 8) out of more than 600 E3 ubiquitin ligases have been used for targeted protein degradation. Each E3 ligase has different expression profiles, labeling efficiencies, and other features that may make them more advantageous to use for drug development:
- Expression profile (image below)
- Can a ligand be made against the E3 ligase?
- Are pockets of the E3…
