Computational strategies for the design of proteolysis targeting chimera degraders: Artificial intelligence enabled PROTAC design DOI
Rajamanikkam Kamaraj, Radim Nencka, Petr Pávek

et al.

Annual reports in medicinal chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Targeted protein degradation: advances in drug discovery and clinical practice DOI Creative Commons
Guangcai Zhong, Xiaoyu Chang, Weilin Xie

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 6, 2024

Abstract Targeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing stark contrast to traditional approaches like small molecule inhibitors that primarily focus on inhibiting function. This advanced technology capitalizes the cell’s intrinsic proteolytic systems, including proteasome and lysosomal pathways, selectively eliminate disease-causing proteins. TPD not only enhances efficacy of treatments but also expands scope applications. Despite its considerable potential, faces challenges related properties drugs their rational design. review thoroughly explores mechanisms clinical advancements TPD, from initial conceptualization practical implementation, with particular proteolysis-targeting chimeras molecular glues. In addition, delves into emerging technologies methodologies aimed at addressing these enhancing efficacy. We discuss significant trials highlight promising outcomes associated drugs, illustrating potential transform treatment landscape. Furthermore, considers benefits combining other therapies enhance overall effectiveness overcome drug resistance. The future directions applications are explored, presenting an optimistic perspective further innovations. By offering comprehensive overview current innovations faced, this assesses transformative revolutionizing development setting stage for new era medical therapy.

Language: Английский

Citations

14
Current Status of Computational Approaches for Small Molecule Drug Discovery DOI Creative Commons
Weijun Xu

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(21), P. 18633 - 18636

Published: Oct. 24, 2024

2024 has been an exciting year for computational sciences, with the Nobel Prize in Physics awarded "artificial neural network" and Chemistry presented "protein structure prediction design". Given rapid advancements Computer-Aided Drug Design (CADD) Artificial Intelligence Discovery (AIDD), a document summarizing their current standing future directions would be timely relevant to readership of

Language: Английский

Citations

6
Development of PROTACs using computational approaches DOI
Jingxuan Ge,

Chang-Yu Hsieh,

Meijing Fang

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

6
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
Computational approaches to aid PROTAC drug discovery DOI

Sohini Chakraborti,

Kirsten McAulay

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 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
E3 ubiquitin ligases and their therapeutic potential in disease Management DOI
Geet Madhukar, Md Azizul Haque, Shawez Khan

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116875 - 116875

Published: March 1, 2025

Language: Английский

Citations

0
Rational Proteolysis Targeting Chimera Design Driven by Molecular Modeling and Machine Learning DOI
Shuoyan Tan, Zhuo Chen, Ruiqiang Lu

et al.

Wiley Interdisciplinary Reviews Computational Molecular Science, Journal Year: 2025, Volume and Issue: 15(2)

Published: March 1, 2025

ABSTRACT Proteolysis targeting chimera (PROTAC) induces specific protein degradation through the ubiquitin–proteasome system and offers significant advantages over small molecule drugs. They are emerging as a promising avenue, particularly in previously “undruggable” targets. Traditional PROTACs have been discovered large‐scale experimental screening. Extensive research efforts focused on unraveling biological pharmacological functions of PROTACs, with strides made toward transitioning from empirical discovery to rational, structure‐based design strategies. This review provides an overview recent representative computer‐aided drug studies PROTACs. We highlight how utilization targeted database, molecular modeling techniques, machine learning algorithms, computational methods contributes facilitating PROTAC discovery. Furthermore, we conclude achievements field explore challenges future directions. aim offer insights references for rational

Language: Английский

Citations

0
Computational strategies for the design of proteolysis targeting chimera degraders: Artificial intelligence enabled PROTAC design DOI
Rajamanikkam Kamaraj, Radim Nencka, Petr Pávek

et al.

Annual reports in medicinal chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0