Traditional drug discovery mainly focuses on direct regulation of protein activity. The
development and application of protein activity modulators, particularly inhibitors, has been …

The interleukin-1 receptor associated kinase 4 (IRAK-4) is a member of serine-threonine
kinase family, which plays an important role in the regulation of interleukin-1 receptors (IL …

Targeted protein degradation via “hijacking” of the ubiquitin-proteasome system using
proteolysis targeting chimeras (PROTACs) has evolved into a novel therapeutic modality …

Carbon–heteroatom bonds, most often amide and ester bonds, are the standard method to
link together two complex fragments because carboxylic acids, amines, and alcohols are …

We report small molecular PROTAC compounds targeting the androgen receptor N-terminal
domain (AR-NTD), which were obtained by tethering AR-NTD antagonists and different …

Background Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein
43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron …

Ubiquitination is a key post-translational modification of proteins, affecting the regulation of
multiple cellular processes. Cells are equipped with over 600 ubiquitin orchestrators, called …

Despite significant efficacy, one of the major limitations of small-molecule Bruton's tyrosine
kinase (BTK) agents is the presence of clinically acquired resistance, which remains a major …

Inducing protein degradation by proteolysis targeting chimeras has gained tremendous
momentum as a promising novel therapeutic strategy. Here, we report the design, synthesis …

Glutarimides such as thalidomide, pomalidomide, and lenalidomide are the most frequently
used ligands to recruit E3 ubiquitin ligase cereblon (CRBN) for the development of …