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 …

Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

TB Faust, H Yoon, RP Nowak, KA Donovan, Z Li… - Nature chemical …, 2020 - nature.com
The investigational drugs E7820, indisulam and tasisulam (aryl-sulfonamides) promote the
degradation of the splicing factor RBM39 in a proteasome-dependent mechanism. While the …

Emerging strategies for prospective discovery of molecular glue degraders

B Wang, S Cao, N Zheng - Current Opinion in Structural Biology, 2024 - Elsevier
Molecular glue (MG) degraders are monovalent small molecule compounds that co-opt E3
ubiquitin ligases to target neo-substrates for proteasomal degradation. Here, we provide a …

Novel mechanisms of molecular glue-induced protein degradation

S Alabi - Biochemistry, 2021 - ACS Publications
Molecular glues, as defined thus far in the targeted protein degradation (TPD) field, are
monovalent small molecules (< 500 Da) that reshape the surface of an E3 ligase receptor …

[HTML][HTML] Template-assisted covalent modification of DCAF16 underlies activity of BRD4 molecular glue degraders

YD Li, MW Ma, MM Hassan, M Hunkeler, M Teng… - BioRxiv, 2023 - ncbi.nlm.nih.gov
Small molecules that induce protein-protein interactions to exert proximity-driven
pharmacology such as targeted protein degradation are a powerful class of therapeutics 1 …

Molecular glues for targeted protein degradation: from serendipity to rational discovery

G Dong, Y Ding, S He, C Sheng - Journal of medicinal chemistry, 2021 - ACS Publications
Targeted protein degradation is a promising area in the discovery and development of
innovative therapeutics. Molecular glues mediate proximity-induced protein degradation and …

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 …

Template-assisted covalent modification underlies activity of covalent molecular glues

YD Li, MW Ma, MM Hassan, M Hunkeler… - Nature Chemical …, 2024 - nature.com
Molecular glues are proximity-inducing small molecules that have emerged as an attractive
therapeutic approach. However, developing molecular glues remains challenging, requiring …

Molecular glues: the adhesive connecting targeted protein degradation to the clinic

JM Sasso, R Tenchov, DS Wang, LS Johnson… - Biochemistry, 2022 - ACS Publications
Targeted protein degradation is a rapidly exploding drug discovery strategy that uses small
molecules to recruit disease-causing proteins for rapid destruction mainly via the ubiquitin …

Haven't got a glue: protein surface variation for the design of molecular glue degraders

Z Kozicka, NH Thomä - Cell Chemical Biology, 2021 - cell.com
Molecular glue degraders are small, drug-like compounds that induce interactions between
an E3 ubiquitin ligase and a target, which result in ubiquitination and subsequent …