Proximity-based modalities for biology and medicine
Molecular proximity orchestrates biological function, and blocking existing proximities is an
established therapeutic strategy. By contrast, strengthening or creating neoproximity with …
established therapeutic strategy. By contrast, strengthening or creating neoproximity with …
From thalidomide to rational molecular glue design for targeted protein degradation
Thalidomide and its derivatives are powerful cancer therapeutics that are among the best-
understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 …
understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 …
DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic-and acquired-degrader resistance
M Schröder, M Renatus, X Liang, F Meili… - Nature …, 2024 - nature.com
Targeted protein degradation (TPD) mediates protein level through small molecule induced
redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal …
redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal …
Discovery of molecular glue degraders via isogenic morphological profiling
A Ng, F Offensperger, JA Cisneros… - ACS Chemical …, 2023 - ACS Publications
Molecular glue degraders (MGDs) are small molecules that degrade proteins of interest via
the ubiquitin–proteasome system. While MGDs were historically discovered serendipitously …
the ubiquitin–proteasome system. While MGDs were historically discovered serendipitously …
E3-specific degrader discovery by dynamic tracing of substrate receptor abundance
Targeted protein degradation (TPD) is a new pharmacology based on small-molecule
degraders that induce proximity between a protein of interest (POI) and an E3 ubiquitin …
degraders that induce proximity between a protein of interest (POI) and an E3 ubiquitin …
Base editor screens for in situ mutational scanning at scale
A fundamental challenge in biology is understanding the molecular details of protein
function. How mutations alter protein activity, regulation, and response to drugs is of critical …
function. How mutations alter protein activity, regulation, and response to drugs is of critical …
Induced protein degradation for therapeutics: past, present, and future
The concept of induced protein degradation by small molecules has emerged as a
promising therapeutic strategy that is particularly effective in targeting proteins previously …
promising therapeutic strategy that is particularly effective in targeting proteins previously …
Advancing targeted protein degradation via multiomics profiling and artificial intelligence
M Duran-Frigola, M Cigler… - Journal of the American …, 2023 - ACS Publications
Only around 20% of the human proteome is considered to be druggable with small-molecule
antagonists. This leaves some of the most compelling therapeutic targets outside the reach …
antagonists. This leaves some of the most compelling therapeutic targets outside the reach …
Discovery of a Potent Proteolysis Targeting Chimera Enables Targeting the Scaffolding Functions of FK506‐Binding Protein 51 (FKBP51)
TM Geiger, M Walz, C Meyners, A Kuehn… - Angewandte Chemie …, 2024 - Wiley Online Library
Abstract The FK506‐binding protein 51 (FKBP51) is a promising target in a variety of
disorders including depression, chronic pain, and obesity. Previous FKBP51‐targeting …
disorders including depression, chronic pain, and obesity. Previous FKBP51‐targeting …