Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …

Abstract The Ser/Thr kinase mechanistic target of rapamycin (mTOR) is a central regulator of
cellular metabolism. As part of mTOR complex 1 (mTORC1), mTOR integrates signals such …

Molecular proximity orchestrates biological function, and blocking existing proximities is an
established therapeutic strategy. By contrast, strengthening or creating neoproximity with …

Targeted protein degradation is a promising area in the discovery and development of
innovative therapeutics. Molecular glues mediate proximity-induced protein degradation and …

2021 marks the 30th anniversary of the revelation that cyclosporin A and FK506 act in a way
previously not seen—as" molecular glues" that induce neo-protein–protein associations. As …

The discovery of small-molecule inhibitors requires suitable binding pockets on protein
surfaces. Proteins that lack this feature are considered undruggable and require innovative …

Protein–protein interactions (PPIs) govern all biological processes. Some small molecules
modulate PPIs through induced protein proximity. In particular, molecular glue degraders …

Targeted protein degradation (TPD) provides unprecedented opportunities for drug
discovery. While the proteolysis-targeting chimera (PROTAC) technology has already …

Vaccine-mediated immunity often relies on the generation of protective antibodies and
memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth …

In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with
efforts to understand the mechanism of action of the drug rapamycin, which∼ 25 y ago led to …