Although no longer a public health emergency of international concern, COVID-19 remains
a persistent and critical health concern. The development of effective antiviral drugs could …

Degrader technologies, which enable the chemical knockdown of disease-causing proteins,
are promising for drug discovery. After two decades of research, degraders using the …

Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation
to hypoxia in humans. The HIF-1α protein level and activity are tightly regulated by the …

Small cell lung cancer (SCLC) has limited therapeutic options and an exceptionally poor
prognosis. Understanding the oncogenic drivers of SCLC may help define novel therapeutic …

Class I phosphoinositide 3-kinases (PI3Ks) control cellular growth, but are also essential in
insulin signaling and glucose homeostasis. Pan-PI3K inhibitors thus generate substantial …

PROteolysis TArgeting Chimaeras (PROTACs) offer new opportunities in modern medicine
by targeting proteins that are undruggable to classic inhibitors. However, due to their …

Conditional control of protein expression facilitates studies of nuclear functions, which are
highly dynamic and tightly linked to the cell cycle in proliferating cells. However, conditional …

The success of inhibitor-based therapeutics is largely constrained by the acquisition of
therapeutic resistance, which is partially driven by the undruggable proteome. The …

Starting from a nonselective bromodomain and extraterminal (BET) inhibitor and a cereblon
ligand, we have used precise conformational control for the development of two potent and …

Targeted degradation of proteins by chimeric heterobifunctional degraders has emerged as
a major drug discovery paradigm. Despite the increased interest in this approach, the criteria …