Polymer Journal, Год журнала: 2024, Номер 57(1), С. 119 - 128
Опубликована: Сен. 19, 2024
Язык: Английский
Coordination Chemistry Reviews, Год журнала: 2023, Номер 501, С. 215560 - 215560
Опубликована: Ноя. 27, 2023
Язык: Английский
Процитировано
60
Journal of the American Chemical Society, Год журнала: 2024, Номер 146(9), С. 6252 - 6265
Опубликована: Фев. 20, 2024
Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation administered stages separated by dark intervals permit recovery during these breaks. However, current photosensitizers used incapable sustaining ROS production intervals, leading suboptimal outcomes (Table S1). circumvent drawback, we have synthesized novel photosensitizer based on triple-anthracene derivative designed prolonged generation, even after cessation exposure. Our study reveals unique action derivatives, facilitating direct and effective disruption biomolecules significantly improving efficacy S2). Moreover, existing lack imaging capabilities monitoring, constraints fine-tuning parameters also serves as an afterglow agent, emitting sustained luminescence postirradiation. This function allows precise optimization between sessions aids determining timing subsequent irradiation, thus enabling meticulous control over parameters. Utilizing our photosensitizer, formulated regimen effectively eliminates orthotopic pancreatic tumors. investigation highlights promise employing long-persistent activity advanced approaches overcome limitations tumor treatment.
Язык: Английский
Процитировано
39
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Май 21, 2024
Abstract Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit endogenous E3 ubiquitin ligases facilitate degradation of interest (POIs) through ubiquitin–proteasome system (UPS) in cyclic catalytic manner. Despite recent endeavors advance utilization clinical settings, majority fail progress beyond preclinical phase drug development. There are multiple factors impeding market entry PROTACs, insufficiently precise favorable POIs standing out as one most formidable obstacles. Recently, there been exploration new-generation advanced including PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, improve vivo efficacy PROTACs. These improved possess capability mitigate undesirable physicochemical characteristics inherent thereby enhancing their targetability reducing off-target side effects. The will mark pivotal turning point realm targeted protein degradation. In this comprehensive review, we meticulously summarized state-of-the-art advancements achieved by these cutting-edge elucidated underlying design principles, deliberated upon prevailing encountered, provided an insightful outlook on future prospects within field.
Язык: Английский
Процитировано
35
European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 276, С. 116725 - 116725
Опубликована: Июль 30, 2024
Язык: Английский
Процитировано
27
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Ноя. 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.
Язык: Английский
Процитировано
26
Nanoscale, Год журнала: 2024, Номер 16(9), С. 4378 - 4391
Опубликована: Янв. 1, 2024
Schematic illustration of the combinational strategy nanotechnology and PROTACs (Nano-PROTACs): typical shortcomings traditional nanotechnology-based strategies for PROTAC drugs optimization.
Язык: Английский
Процитировано
23
Coordination Chemistry Reviews, Год журнала: 2024, Номер 510, С. 215863 - 215863
Опубликована: Апрель 5, 2024
Язык: Английский
Процитировано
20
Journal of the American Chemical Society, Год журнала: 2024, Номер 146(15), С. 10753 - 10766
Опубликована: Апрель 5, 2024
Proteolysis targeting chimera (PROTAC) technology is an innovative strategy for cancer therapy, which, however, suffers from poor delivery and limited capability protein of interest (POI) degradation. Here, we report a the in situ formulation antineoplastic Supra-PROTACs via intracellular sulfatase-responsive assembly peptides. Coassembling sulfated peptide with two ligands binding to ubiquitin VHL Bcl-xL leads formation pro-Supra-PROTAC, which ratio rationally optimized based on their affinity. The resulting pro-Supra-PROTAC precisely undergoes enzyme-responsive into nanofibrous cells overexpressing sulfatase. Mechanistic studies reveal that pro-Supra-PROTACs selectively cause apparent cytotoxicity through degradation activation caspase-dependent apoptosis, during ligand improves bioactivity POI cell death. In vivo show enhanced tumor accumulation retention pro-Supra-PROTACs, as well inhibiting growth excellent biosafety when coadministrating chemodrugs. Our findings provide new approach enzyme-regulated peptides living development PROTACs high delivering efficiency.
Язык: Английский
Процитировано
20
Chemical Science, Год журнала: 2024, Номер 15(31), С. 12234 - 12257
Опубликована: Янв. 1, 2024
Photodynamic therapy (PDT) has been developed as a potential cancer treatment approach owing to its non-invasiveness, spatiotemporal control and limited side effects. Currently, great efforts have made improve the PDT effect in terms of safety efficiency. In this review, we highlight recent advances innovative strategies for enhanced PDT, including (1) development novel radicals, (2) design activatable photosensitizers based on TME light, (3) photocatalytic NADH oxidation damage mitochondrial electron transport chain. Additionally, new mechanisms are also presented an inspiration PSs. Finally, discuss current challenges future prospects clinical practice these strategies. It is hoped that review will provide angle understanding relationship between intratumoural redox environment mechanisms, ideas smart systems.
Язык: Английский
Процитировано
19
Biochemistry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 10, 2025
Proteolysis-targeting chimeras (PROTACs) represent a transformative advancement in drug discovery, offering method to degrade specific intracellular proteins. Unlike traditional inhibitors, PROTACs are bifunctional molecules that target proteins for elimination, enabling the potential treatment of previously "undruggable" This concept, pioneered by Crews and his team, introduced use small link protein an E3 ubiquitin ligase, inducing ubiquitination subsequent degradation protein. By promoting rather than merely inhibiting function, present novel therapeutic strategy with enhanced specificity effectiveness, especially areas such as cancer neurodegenerative diseases. Since their initial field PROTAC research has rapidly expanded numerous now designed wide range disease-relevant The substantial research, investment, collaboration across academia pharmaceutical industry reflect growing interest PROTACs. Review discusses journey from discovery clinical trials, highlighting advancements challenges. Additionally, recent developments fluorescent photogenic PROTACs, used real-time tracking degradation, presented, showcasing evolving targeted therapy.
Язык: Английский
Процитировано
6