Conquering PROTAC molecular design and drugability DOI
Ritesh P. Bhole,

Sonali Labhade,

Shailendra Gurav

et al.

Bioanalysis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: March 20, 2025

PROTACs are reshaping drug discovery by enabling targeted protein degradation, overcoming the limitations of traditional inhibitors, and addressing previously "undruggable" proteins. The present perspective explores advancements in PROTAC molecular design, focusing on ligand discovery, E3 ligase recruitment, ternary complex optimization. Integrating AI-driven modeling, FBDD, SBDD accelerates development. In contrast, emerging innovations, such as PHOTACs, hypoxia-responsive systems, Ab-PROTACs, enhance precision reduce systemic toxicity. Clinical successes, including ARV-110 for castration-resistant prostate cancer ARV-471 breast cancer, exemplify their ability to overcome resistance provide durable effects. expanding into neurodegenerative diseases rare conditions, highlighting versatility. By challenges pharmacokinetics, safety, scalability, poised revolutionize medicine. This article presents a forward-looking conquering design drugability PROTACs, paving path transformative therapies.

Language: Английский

PROTACs in the treatment of viral diseases DOI Creative Commons
Ritesh P. Bhole, Payal R. Kute, Shailendra Gurav

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 17(3), P. 267 - 269

Published: Jan. 15, 2025

KEYWORDS: PROTACsAntiviral therapyUbiquitin-proteasome systemUndruggable targetsDrug resistanceIndomethacin-based PROTACsViral diseasesPROTACs in clinical trials

Language: Английский

Citations

1
Conquering PROTAC molecular design and drugability DOI
Ritesh P. Bhole,

Sonali Labhade,

Shailendra Gurav

et al.

Bioanalysis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: March 20, 2025

PROTACs are reshaping drug discovery by enabling targeted protein degradation, overcoming the limitations of traditional inhibitors, and addressing previously "undruggable" proteins. The present perspective explores advancements in PROTAC molecular design, focusing on ligand discovery, E3 ligase recruitment, ternary complex optimization. Integrating AI-driven modeling, FBDD, SBDD accelerates development. In contrast, emerging innovations, such as PHOTACs, hypoxia-responsive systems, Ab-PROTACs, enhance precision reduce systemic toxicity. Clinical successes, including ARV-110 for castration-resistant prostate cancer ARV-471 breast cancer, exemplify their ability to overcome resistance provide durable effects. expanding into neurodegenerative diseases rare conditions, highlighting versatility. By challenges pharmacokinetics, safety, scalability, poised revolutionize medicine. This article presents a forward-looking conquering design drugability PROTACs, paving path transformative therapies.

Language: Английский

Citations

0