Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(16), P. 7066 - 7114
Published: Jan. 1, 2022
Proteolysis targeting chimeras (PROTACs) technology is a novel and promising therapeutic strategy using small molecules to induce ubiquitin-dependent degradation of proteins.
Language: Английский
Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 102 - 114
Published: Jan. 16, 2020
Language: Английский
Citations
780
Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(12), P. 949 - 963
Published: Oct. 30, 2019
Language: Английский
Citations
718
Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)
Published: Dec. 24, 2019
Although many kinds of therapies are applied in the clinic, drug-resistance is a major and unavoidable problem. Another disturbing statistic limited number drug targets, which presently only 20-25% all protein targets that currently being studied. Moreover, focus current explorations their enzymatic functions, ignores functions from scaffold moiety. As promising appealing technology, PROteolysis TArgeting Chimeras (PROTACs) have attracted great attention both academia industry for finding available approaches to solve above problems. PROTACs regulate function by degrading target proteins instead inhibiting them, providing more sensitivity drug-resistant greater chance affect nonenzymatic functions. been proven show better selectivity compared classic inhibitors. can be described as chemical knockdown approach with rapidity reversibility, presents new different biology other gene editing tools avoiding misinterpretations arise potential genetic compensation and/or spontaneous mutations. PRTOACs widely explored throughout world outperformed not cancer diseases, but also immune disorders, viral infections neurodegenerative diseases. present very powerful crossing hurdles discovery tool development biology, efforts needed gain get deeper insight into efficacy safety clinic. More binders E3 ligases applicable developing waiting exploration.
Language: Английский
Citations
513
Nature Medicine, Journal Year: 2019, Volume and Issue: 25(12), P. 1938 - 1947
Published: Dec. 1, 2019
Language: Английский
Citations
503
Current Opinion in Chemical Biology, Journal Year: 2019, Volume and Issue: 50, P. 111 - 119
Published: April 17, 2019
Language: Английский
Citations
481
Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(10), P. 638 - 654
Published: June 15, 2021
Language: Английский
Citations
435
Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(12), P. 5214 - 5236
Published: Jan. 1, 2022
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules consisting of one ligand that binds to a protein interest (POI) and another can recruit an E3 ubiquitin ligase. The chemically-induced proximity between the POI ligase results in ubiquitination subsequent degradation by ubiquitin-proteasome system (UPS). event-driven mechanism action (MOA) PROTACs offers several advantages compared traditional occupancy-driven small molecule inhibitors, such as catalytic nature, reduced dosing frequency, more potent longer-lasting effect, added layer selectivity reduce potential toxicity, efficacy face drug-resistance mechanisms, targeting nonenzymatic functions, expanded target space. Here, we highlight important milestones briefly discuss lessons learned about targeted (TPD) recent years conjecture on efforts still needed expand toolbox for PROTAC discovery ultimately provide promising therapeutics.
Language: Английский
Citations
425
Nature Chemical Biology, Journal Year: 2019, Volume and Issue: 15(10), P. 937 - 944
Published: Sept. 16, 2019
Language: Английский
Citations
388
Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(4), P. 265 - 278
Published: Feb. 13, 2023
Language: Английский
Citations
343
Cell chemical biology, Journal Year: 2020, Volume and Issue: 27(8), P. 998 - 1014
Published: Aug. 1, 2020
Language: Английский
Citations
336