The current predominant therapeutic paradigm is based on maximizing drug-receptor
occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug …

Inhibiting protein function selectively is a major goal of modern drug discovery. Here, we
report a previously understudied benefit of small molecule proteolysis-targeting chimeras (…

Proteolysis targeting chimera (PROTAC) technology has emerged over the last two decades
as a powerful tool for targeted degradation of endogenous proteins. Herein we describe the …

Protein homeostasis networks are highly regulated systems responsible for maintaining the
health and productivity of cells. Whereas therapeutics have been developed to disrupt …

… DP Bondeson is supported by an NCI Predoctoral to Postdoctoral Fellow Transition
award (F99 CA212229-02). CM Crews gratefully acknowledges the US NIH for their support (…

Conditional degron tags (CDTs) are a powerful tool for target validation that combines the
kinetics and reversible action of pharmacological agents with the generalizability of genetic …

Nephrolithiasis is a major public health problem with a complex and varied etiology. Most
stones are composed of calcium oxalate (CaOx), with dietary excess a risk factor. Because of …

Despite advances in precision medicine, the clinical prospects for patients with ovarian and
uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR–…

Herein we employ a scaffold hopping approach to enhance the activity of a previously
reported BCR-Abl PROTAC. This represents a significant advance in the PROTAC field since it …

The gut and Malpighian tubules of insects are the primary sites of active solute and water
transport for controlling hemolymph and urine composition, pH, and osmolarity. These …