Advancing target validation with PROTAC technology DOI
Margaret Spitz,

Aseel Kashkush,

Raphael I. Benhamou

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Targeted protein degradation (TPD) is a cutting-edge technology that provides new avenues for drug discovery and development. PROteolysis TArgeting Chimeras (PROTACs) are the most established advanced TPD strategy, enabling selective of disease-associated 'undruggable' proteins interest (POIs) by leveraging cell's natural machinery. To confirm PROTAC-induced proximity drives degradation, target validation ternary complex formation must be thoroughly assessed. In this perspective, authors detail some widely used in silico, structural, vitro, cellulo methods to validate PROTAC engagement formation. Additionally, they discuss growing use PROTACs as chemical probes novel identification validation. Target essential approach, ongoing studies should prioritize confirming using assays conducted under physiologically relevant cellular conditions. The believe proteomics analyses among valuable tools elucidating mechanism, selectivity, outcomes PROTACs. They also remain optimistic about future development their engagement. While rapidly advancing, it still holds vast opportunities exploration, offering significant potential further both biological research drive drugs.

Language: Английский

Innovative Protein Degraders for Targeted Cancer and Viral Therapy DOI Creative Commons
Robert B. Kargbo

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(2), P. 222 - 223

Published: Jan. 29, 2025

The development of targeted protein degraders offers novel strategies for treating cancer and chronic viral infections. This Patent Highlight integrates bifunctional degraders, leveraging autophagy via p62, substituted oxazolone compounds targeting IKZF1–4 transcription factors. These demonstrate exceptional efficacy in degrading pathogenic proteins, reprogramming immune responses, facilitating tumor immunity. dual approach underscores the potential cellular degradation systems precision medicine.

Language: Английский

Citations

0
In silico modeling of targeted protein degradation DOI Creative Commons
Wenxing Lv,

Xiaojuan Jia,

Bowen Tang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117432 - 117432

Published: Feb. 20, 2025

Language: Английский

Citations

0
A Comprehensive Primer and Review of PROTACs and Their In Silico Design DOI Creative Commons

Jacopo Zattoni,

Paola Vottero,

Gea Carena

et al.

Computer Methods and Programs in Biomedicine, Journal Year: 2025, Volume and Issue: 264, P. 108687 - 108687

Published: Feb. 27, 2025

Language: Английский

Citations

0
Advancing target validation with PROTAC technology DOI
Margaret Spitz,

Aseel Kashkush,

Raphael I. Benhamou

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Targeted protein degradation (TPD) is a cutting-edge technology that provides new avenues for drug discovery and development. PROteolysis TArgeting Chimeras (PROTACs) are the most established advanced TPD strategy, enabling selective of disease-associated 'undruggable' proteins interest (POIs) by leveraging cell's natural machinery. To confirm PROTAC-induced proximity drives degradation, target validation ternary complex formation must be thoroughly assessed. In this perspective, authors detail some widely used in silico, structural, vitro, cellulo methods to validate PROTAC engagement formation. Additionally, they discuss growing use PROTACs as chemical probes novel identification validation. Target essential approach, ongoing studies should prioritize confirming using assays conducted under physiologically relevant cellular conditions. The believe proteomics analyses among valuable tools elucidating mechanism, selectivity, outcomes PROTACs. They also remain optimistic about future development their engagement. While rapidly advancing, it still holds vast opportunities exploration, offering significant potential further both biological research drive drugs.

Language: Английский

Citations

0