Precision-engineered PROTACs minimize off-tissue effects in cancer therapy DOI Creative Commons

Jianghua Shi,

Luo Wang,

Xuanwei Zeng

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Ноя. 22, 2024

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain major challenge, leading toxicity healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated tumor environments, E3 ligase overexpression strategies. Innovations such as PEGylation nanotechnology also play role optimizing efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges translation.

Язык: Английский

PROTAC-Based Therapeutics for Targeting HPV Oncoproteins in Head and Neck Cancers DOI Creative Commons
Nobendu Mukerjee, Dibyendu Mukherjee

Nano TransMed, Год журнала: 2025, Номер unknown, С. 100071 - 100071

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2

CRBN‐PROTACs in Cancer Therapy: From Mechanistic Insights to Clinical Applications DOI Open Access
Riya Thapa, Asif Ahmad Bhat, Gaurav Gupta

и другие.

Chemical Biology & Drug Design, Год журнала: 2024, Номер 104(5)

Опубликована: Ноя. 1, 2024

Cereblon (CRBN), a member of the E3 ubiquitin ligase complex, has gained significant attention as therapeutic target in cancer. CRBN regulates degradation various proteins cancer progression, including transcription factors and signaling molecules. PROTACs (proteolysis-targeting chimeras) are novel approach that uses cell's system to remove disease-causing selectively. CRBN-dependent work by tagging harmful for destruction through ubiquitin-proteasome system. This strategy offers several advantages over traditional protein inhibition methods, potential overcome drug resistance. Recent progress developing CRBN-based shown promising preclinical results both hematologic malignancies solid tumors. Additionally, have enhanced our understanding CRBN's role cancer, potentially serving biomarkers patient stratification predicting responses. In this review, we delineate mechanisms action (CRBN-PROTACs), summarize recent advances clinical applications, provide perspective on future development.

Язык: Английский

Процитировано

4

Prodrug Approach as a Strategy to Enhance Drug Permeability DOI Creative Commons
Mariana Moraes Dionysio de Souza, Ana Luísa Rodriguez Gini,

Jhonnathan Alves Moura

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 297 - 297

Опубликована: Фев. 21, 2025

Absorption and permeability are critical physicochemical parameters that must be balanced to achieve optimal drug uptake. These key factors closely linked the maximum absorbable dose required provide appropriate plasma levels of drugs. Among various strategies employed enhance solubility permeability, prodrug design stands out as a highly effective versatile approach for improving properties enabling optimization biopharmaceutical pharmacokinetic while mitigating adverse effects. Prodrugs compounds with reduced or no activity that, through bio-reversible chemical enzymatic processes, release an active parental drug. The application this technology has led significant advancements in during phase, it offers broad potential further development. Notably, approximately 13% drugs approved by U.S. Food Drug Administration (FDA) between 2012 2022 were prodrugs. In review article, we will explore describing examples market We also describe use optimize PROteolysis TArgeting Chimeras (PROTACs) using conjugation technologies. highlight some new technologies prodrugs enrich properties, contributing developing safe

Язык: Английский

Процитировано

0

Research progress of ATR small molecule inhibitors in cancer therapy DOI
Shujin Guo, Q. He, Yuping Liu

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 296, С. 117804 - 117804

Опубликована: Май 24, 2025

Язык: Английский

Процитировано

0

Precision-engineered PROTACs minimize off-tissue effects in cancer therapy DOI Creative Commons

Jianghua Shi,

Luo Wang,

Xuanwei Zeng

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Ноя. 22, 2024

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain major challenge, leading toxicity healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated tumor environments, E3 ligase overexpression strategies. Innovations such as PEGylation nanotechnology also play role optimizing efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges translation.

Язык: Английский

Процитировано

0