Protein degraders enter the clinic—a new approach to cancer therapy
D Chirnomas, KR Hornberger, CM Crews - Nature Reviews Clinical …, 2023 - nature.com
Heterobifunctional protein degraders, such as PROteolysis TArgeting Chimera (PROTAC)
protein degraders, constitute a novel therapeutic modality that harnesses the cell's natural …
protein degraders, constitute a novel therapeutic modality that harnesses the cell's natural …
PROTAC targeted protein degraders: the past is prologue
Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …
tackle disease-causing proteins that have historically been highly challenging to target with …
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 …
Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders
The von Hippel-Lindau (VHL) Cullin RING E3 ligase is an essential enzyme in the ubiquitin-
proteasome system that recruits substrates such as the hypoxia inducible factor for …
proteasome system that recruits substrates such as the hypoxia inducible factor for …
DNA-encoded chemical libraries
AL Satz, A Brunschweiger, ME Flanagan… - Nature Reviews …, 2022 - nature.com
DNA-encoded chemical library (DECL) technology is used by the pharmaceutical industry to
discover small molecules capable of modulating biologically relevant targets. DECL …
discover small molecules capable of modulating biologically relevant targets. DECL …
Discovery of XL01126: a potent, fast, cooperative, selective, orally bioavailable, and blood–brain barrier penetrant PROTAC degrader of leucine-rich repeat kinase 2
X Liu, AF Kalogeropulou, S Domingos… - Journal of the …, 2022 - ACS Publications
Leucine-rich repeat kinase 2 (LRRK2) is one of the most promising targets for Parkinson's
disease. LRRK2-targeting strategies have primarily focused on type 1 kinase inhibitors …
disease. LRRK2-targeting strategies have primarily focused on type 1 kinase inhibitors …
Recent developments in PROTAC‐mediated protein degradation: from bench to clinic
Abstract Proteolysis‐targeting chimeras (PROTACs), an emerging paradigm‐shifting
technology, hijacks the ubiquitin‐proteasome system for targeted protein degradation …
technology, hijacks the ubiquitin‐proteasome system for targeted protein degradation …
E3 ligase ligand chemistries: from building blocks to protein degraders
In recent years, proteolysis-targeting chimeras (PROTACs), capable of achieving targeted
protein degradation, have proven their great therapeutic potential and usefulness as …
protein degradation, have proven their great therapeutic potential and usefulness as …
PROTAC'ing oncoproteins: targeted protein degradation for cancer therapy
Molecularly targeted cancer therapies substantially improve patient outcomes, although the
durability of their effectiveness can be limited. Resistance to these therapies is often related …
durability of their effectiveness can be limited. Resistance to these therapies is often related …