Rational chemical design of molecular glue degraders

ES Toriki, JW Papatzimas, K Nishikawa… - ACS central …, 2023 - ACS Publications
Targeted protein degradation with molecular glue degraders has arisen as a powerful
therapeutic modality for eliminating classically undruggable disease-causing proteins …

Molecular glue concept solidifies

K Baek, BA Schulman - Nature chemical biology, 2020 - nature.com
Molecular-glue-mediated proximity-induced degradation now allows unprecedented
therapeutic targeting of previously undruggable proteins. Structures showing how aryl …

Targeted degradation via direct 26S proteasome recruitment

C Bashore, S Prakash, MC Johnson… - Nature Chemical …, 2023 - nature.com
Engineered destruction of target proteins by recruitment to the cell's degradation machinery
has emerged as a promising strategy in drug discovery. The majority of molecules that …

Harnessing the E3 ligase KEAP1 for targeted protein degradation

J Wei, F Meng, KS Park, H Yim, J Velez… - Journal of the …, 2021 - ACS Publications
Proteolysis targeting chimeras (PROTACs) represent a new class of promising therapeutic
modalities. PROTACs hijack E3 ligases and the ubiquitin-proteasome system (UPS), leading …

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 …

Iterative design and optimization of initially inactive proteolysis targeting chimeras (PROTACs) identify VZ185 as a potent, fast, and selective von Hippel–Lindau (VHL) …

V Zoppi, SJ Hughes, C Maniaci, A Testa… - Journal of medicinal …, 2018 - ACS Publications
Developing PROTACs to redirect the ubiquitination activity of E3 ligases and potently
degrade a target protein within cells can be a lengthy and unpredictable process, and it …

E3-specific degrader discovery by dynamic tracing of substrate receptor abundance

A Hanzl, E Barone, S Bauer, H Yue… - Journal of the …, 2023 - ACS Publications
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 …

Degradation of the BAF complex factor BRD9 by heterobifunctional ligands

D Remillard, DL Buckley, J Paulk… - Angewandte Chemie …, 2017 - Wiley Online Library
The bromodomain‐containing protein BRD9, a subunit of the human BAF (SWI/SNF)
nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer …

Discovery of a novel DCAF1 ligand using a drug–target interaction prediction model: generalizing machine learning to new drug targets

SW Kimani, J Owen, SR Green, F Li, Y Li… - Journal of Chemical …, 2023 - ACS Publications
DCAF1 functions as a substrate recruitment subunit for the RING-type CRL4DCAF1 and the
HECT family EDVPDCAF1 E3 ubiquitin ligases. The WDR domain of DCAF1 serves as a …

Chemical Specification of E3 Ubiquitin Ligase Engagement by Cysteine-Reactive Chemistry

RC Sarott, I You, YD Li, ST Toenjes… - Journal of the …, 2023 - ACS Publications
Targeted protein degradation relies on small molecules that induce new protein–protein
interactions between targets and the cellular protein degradation machinery. Most of these …