GEN Biotechnology, Год журнала: 2023, Номер 2(2), С. 69 - 75
Опубликована: Апрель 1, 2023
Язык: Английский
Molecules, Год журнала: 2023, Номер 28(10), С. 4014 - 4014
Опубликована: Май 10, 2023
A potential therapeutic strategy to treat conditions brought on by the aberrant production of a disease-causing protein is emerging for targeted breakdown using PROTACs technology. Few medications now in use are tiny, component-based and utilize occupancy-driven pharmacology (MOA), which inhibits function short period time temporarily alter it. By utilizing an event-driven MOA, proteolysis-targeting chimeras (PROTACs) technology introduces revolutionary tactic. Small-molecule-based heterobifunctional hijack ubiquitin–proteasome system trigger degradation target protein. The main challenge PROTAC’s development facing find potent, tissue- cell-specific PROTAC compounds with favorable drug-likeness standard safety measures. ways increase efficacy selectivity focus this review. In review, we have highlighted most important discoveries related proteins PROTACs, new approaches boost proteolysis’ effectiveness development, promising future directions medicine.
Язык: Английский
Процитировано
37
Expert Opinion on Drug Discovery, Год журнала: 2024, Номер 19(4), С. 433 - 449
Опубликована: Янв. 19, 2024
Introduction Molecular Glue Degraders (MGDs) is a concept that refers to class of compounds facilitate the interaction between two proteins or molecules within cell. These act as bridge enhances specific Protein-Protein Interactions (PPIs). Over past decade, this technology has gained attention potential strategy target were traditionally considered undruggable using small molecules.
Язык: Английский
Процитировано
8
European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 265, С. 116041 - 116041
Опубликована: Дек. 13, 2023
Язык: Английский
Процитировано
14
Pharmacology & Therapeutics, Год журнала: 2023, Номер 250, С. 108525 - 108525
Опубликована: Сен. 9, 2023
Язык: Английский
Процитировано
12
Chinese Journal of Natural Medicines, Год журнала: 2025, Номер 23(3), С. 286 - 298
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Bioorganic & Medicinal Chemistry, Год журнала: 2023, Номер 96, С. 117514 - 117514
Опубликована: Ноя. 2, 2023
Язык: Английский
Процитировано
9
MedComm, Год журнала: 2024, Номер 5(2)
Опубликована: Фев. 1, 2024
Abstract Proteolysis‐targeting chimeras (PROTACs) are essential bifunctional molecules that target proteins of interest (POIs) for degradation by cellular ubiquitination machinery. Despite significant progress made in understanding PROTACs' functions, their therapeutic potential remains largely untapped. As a result the success highly flexible, scalable, and low‐cost mRNA therapies, as well advantages first generation peptide PROTACs (p‐PROTACs), we present time an engineering (m‐PROTACs) strategy. This design combines von Hippel–Lindau (VHL) recruiting encoding POI‐binding to form m‐PROTAC promote POI degradation. We then performed proof‐of‐concept experiments using two m‐PROTACs targeting cancer‐related proteins, estrogen receptor alpha B‐cell lymphoma‐extra large protein. Our results demonstrated could successfully degrade POIs different cell lines more effectively inhibit proliferation than traditional p‐PROTACs. Moreover, vivo experiment led tumor regression 4T1 mouse xenograft model. finding highlights enormous promising approach targeted protein therapy.
Язык: Английский
Процитировано
3
Cell Death and Disease, Год журнала: 2024, Номер 15(9)
Опубликована: Сен. 30, 2024
Язык: Английский
Процитировано
3
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
3
Journal of Drug Delivery Science and Technology, Год журнала: 2023, Номер 91, С. 105184 - 105184
Опубликована: Ноя. 22, 2023
Язык: Английский
Процитировано
8