Nature Cardiovascular Research, Год журнала: 2024, Номер 3(3), С. 372 - 388
Опубликована: Март 11, 2024
Язык: Английский
Seminars in Cancer Biology, Год журнала: 2022, Номер 86, С. 84 - 106
Опубликована: Авг. 19, 2022
Язык: Английский
Процитировано
63
Cell Metabolism, Год журнала: 2022, Номер 34(1), С. 35 - 58
Опубликована: Янв. 1, 2022
Язык: Английский
Процитировано
60
Cells, Год журнала: 2021, Номер 10(10), С. 2715 - 2715
Опубликована: Окт. 11, 2021
The Hippo pathway is an evolutionary conserved signaling network that regulates essential processes such as organ size, cell proliferation, migration, stemness and apoptosis. Alterations in this are commonly found solid tumors can lead to hyperproliferation, resistance chemotherapy, compensation for mKRAS tumor immune evasion. As the terminal effectors of pathway, transcriptional coactivators YAP1/TAZ transcription factors TEAD1–4 present exciting opportunities pharmacologically modulate biology cancer settings, inflammation regenerative medicine. This review will provide overview progress current strategies directly indirectly target protein–protein interaction (PPI) with across multiple modalities, focus on recent small molecules able selectively bind TEAD, block its autopalmitoylation inhibit YAP1/TAZ–TEAD-dependent cancer.
Язык: Английский
Процитировано
58
Advanced Drug Delivery Reviews, Год журнала: 2022, Номер 188, С. 114442 - 114442
Опубликована: Июль 8, 2022
Язык: Английский
Процитировано
56
GeoHealth, Год журнала: 2022, Номер 6(4)
Опубликована: Апрель 1, 2022
Abstract There is a growing awareness that the large number of environmental pollutants we are exposed to on daily basis causing major health problems. Compared traditional studies focus individual pollutants, there relatively few how mixtures interact. Several have reported relationship between and development cancer, even when pollutant levels below toxicity reference values. The possibility synergistic interactions different could explain low concentrations can cause These intricate molecular occur through wide variety mechanisms, our understanding physiological effects still limited. purpose this paper discuss recent reports address possible types promote cancer development. Our literature suggest key biological pathways frequently implicated in such processes. include increased production reactive oxygen species, activation by cytochrome P450, aryl hydrocarbon receptor signaling, among others. We need understand pathological vulnerability not only relation basic genetics gene expression, but also terms measurable exposure contaminants. mention for significant improvements future using multitude disciplines, as high‐throughput study models, better tools quantifying patients, innovative pharmacological toxicological studies, high‐efficiency computer analysis, which allow us analyze mechanisms mixtures.
Язык: Английский
Процитировано
38
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
Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(39)
Опубликована: Июль 20, 2023
Proteolysis Targeting Chimeras (PROTACs) represent a promising therapeutic modality to address undruggable and resistant issues in drug discovery. However, potential on-target toxicity remains clinically challenging. We developed generalized caging strategy synthesize series of stimuli-responsive PROTACs (sr-PROTACs) with diverse molecular blocks bearing robust cleavable linkers, presenting "turn on" features manipulating protein degradation. By leveraging pathological cues, such as elevated ROS, phosphatase, H2 S, or hypoxia, external triggers, ultraviolet light, X-Ray, bioorthogonal reagents, we achieved site-specific activation traceless release original through de-caging subsequent self-immolative cleavage, realizing selective uptake controlled degradation vitro. An vivo study revealed that two sr-PROTACs phosphate- fluorine-containing cages exhibited high solubility long plasma exposure, which were specifically activated by tumor overexpressing phosphatase low dosage X-Ray irradiation situ, leading efficient potent remission. With more reactive biomarkers be screened from clinical practice, our library could provide general tool design activatable PROTACs, prodrugs, antibody-drug conjugates, smart biomaterials for personalized treatment, tissue engineering regenerative medicine.
Язык: Английский
Процитировано
33
Cell Death and Disease, Год журнала: 2023, Номер 14(10)
Опубликована: Окт. 27, 2023
Abstract FOXO family of proteins are transcription factors involved in many physiological and pathological processes including cellular homeostasis, stem cell maintenance, cancer, metabolic, cardiovascular diseases. Genetic evidence has been accumulating to suggest a prominent role FOXOs lifespan regulation animal systems from hydra, C elegans, Drosophila, mice. Together with the observation that FOXO3 is second most replicated gene associated extreme human longevity suggests pharmacological targeting can be promising approach treat cancer other age-related diseases extend life health span. However, due broad range functions members FOXO1, 3, 4, 6, isoform-specific might lead greater benefits cause fewer side effects. Therefore, deeper understanding common specific features these as well their redundant our cells represents basis strategies. In this review, we provide an overview evolution, structure, function, disease-relevance each members.
Язык: Английский
Процитировано
33
Nature Chemical Biology, Год журнала: 2023, Номер 19(12), С. 1480 - 1491
Опубликована: Июнь 15, 2023
Язык: Английский
Процитировано
30
Cancers, Год журнала: 2023, Номер 15(13), С. 3506 - 3506
Опубликована: Июль 5, 2023
Cancer represents a significant and persistent global health burden, with its impact underscored by prevalence devastating consequences. Whereas numerous oncogenes could contribute to cancer development, group of transcription factors (TFs) are overactive in the majority tumors. Targeting these TFs may also combat downstream activated TFs, making them attractive potential targets for effective antitumor therapeutic strategy. One such TF is yin yang 1 (YY1), which plays crucial roles development progression various In preclinical studies, YY1 inhibition has shown efficacy inhibiting tumor growth, promoting apoptosis, sensitizing cells chemotherapy. Recent studies have revealed combining immunotherapy enhanced effects. However, clinical translation YY1-targeted therapy still faces challenges drug specificity delivery. This review provides an overview biology, role progression, as well strategies explored therapy, focus on their implications, including those using small molecule inhibitors, RNA interference, gene editing techniques. Finally, we discuss current limitations targeting need further research this area.
Язык: Английский
Процитировано
30