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 …
Advancing targeted protein degradation for cancer therapy
The human proteome contains approximately 20,000 proteins, and it is estimated that more
than 600 of them are functionally important for various types of cancers, including nearly 400 …
than 600 of them are functionally important for various types of cancers, including nearly 400 …
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 …
Target and tissue selectivity of PROTAC degraders
RG Guenette, SW Yang, J Min, B Pei… - Chemical Society …, 2022 - pubs.rsc.org
Targeted protein degradation (TPD) strategies have revolutionized how scientists tackle
challenging protein targets deemed undruggable with traditional small molecule inhibitors …
challenging protein targets deemed undruggable with traditional small molecule inhibitors …
The PROTACtable genome
Proteolysis-targeting chimeras (PROTACs) are an emerging drug modality that may offer
new opportunities to circumvent some of the limitations associated with traditional small …
new opportunities to circumvent some of the limitations associated with traditional small …
A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo
Targeted protein degradation offers an alternative modality to classical inhibition and holds
the promise of addressing previously undruggable targets to provide novel therapeutic …
the promise of addressing previously undruggable targets to provide novel therapeutic …
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 …
Direct-to-biology accelerates PROTAC synthesis and the evaluation of linker effects on permeability and degradation
CE Hendrick, JR Jorgensen, C Chaudhry… - ACS medicinal …, 2022 - ACS Publications
A platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) has been
developed using a direct-to-biology (D2B) approach with a focus on linker effects. A large …
developed using a direct-to-biology (D2B) approach with a focus on linker effects. A large …
Degrader-antibody conjugates
PS Dragovich - Chemical Society Reviews, 2022 - pubs.rsc.org
Degrader-antibody conjugates (DACs) are novel entities that combine a proteolysis
targeting chimera (PROTAC) payload with a monoclonal antibody via some type of chemical …
targeting chimera (PROTAC) payload with a monoclonal antibody via some type of chemical …