Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So fa ...
Molecular glues are small drug-like molecules that induce de novo protein-protein interactions or facilitate pre-existing weak interactions between proteins. In the context of a ubiquitin ligase, such binding events frequently result in ubiquitination by p ...
Pioneer transcription factors (TFs) engage chromatinized DNA motifs. However, it is unclear how the resultant TF-nucleosome complexes are decoded by co-factors. In humans, the TF p53 regulates cell-cycle progression, apoptosis, and the DNA damage response, ...
A multidisciplinary platform is presented to address aryl hydrocarbon receptor (AhR) modulation. A rewired Yonemitsu multicomponent reaction with indole 2-carboxaldehydes and nucleophilic species was designed to access a family of 6-substituted indolocarba ...
Niclosamide, an FDA-approved anthelmintic drug, known to uncouple the mitochondria induces cyclin D1 degradation via CRL4 AMBRA1 . We find a striking correlation between the two processes and that it is observed amongst various compounds. ...