Life Sciences, Journal Year: 2024, Volume and Issue: 356, P. 123031 - 123031
Published: Sept. 1, 2024
Language: Английский
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116725 - 116725
Published: July 30, 2024
Language: Английский
Citations
21
Acta Materia Medica, Journal Year: 2024, Volume and Issue: 3(1)
Published: Jan. 1, 2024
PROTAC, as a novel therapeutic drug model, has received widespread attention from the academic and pharmaceutical industries. At same time, PROTAC technology led many researchers to focus on developing chemical biology tool properties due its unique operating mechanism protein dynamic regulatory properties. In recent years, rapid development of gradually made it an essential for target identification validation. To further promote application tools in discovery basic medical sciences research, this review distinguished between validation concepts. It summarized research progress these aspects.
Language: Английский
Citations
6
Medical Review, Journal Year: 2025, Volume and Issue: unknown
Published: March 5, 2025
Abstract Natural products, the most important chemical library with magical structures and unique functions, have long been playing significant roles in contributing to discovery of novel drugs. The complexity diversity natural products present great challenges regarding exploration their potential targets. Identifying targets not only enhances our understanding biological functions molecular mechanisms, but also paves way for discovering lead compounds disease treatment. Recent advances technologies like biology, structural artificial intelligence provided powerful tools pinpointing product target unraveling mechanisms. This review aims comprehensively summarize innovative strategies employed recent years identify targets, evaluate impact on pathways by modulating pharmacological effects. Moreover, we discuss encountered this field outline future research prospects, aiming offer guidance researchers biology.
Language: Английский
Citations
0
Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 116829 - 116829
Published: March 1, 2025
Language: Английский
Citations
0
Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)
Published: March 31, 2025
Osteoporosis and kidney stones share several common pathophysiological risk factors, their association is well-established. However, previous studies have primarily focused on environmental mediators, such as diet, the precise mechanism linking these two conditions remains unclear. The relationship between osteoporosis was analyzed using weighted multivariate logistic regression, employing data from five cycles of National Health Nutrition Examination Survey (NHANES) 2007–2010, 2013–2014, 2017–2020. Gene expression Expression Omnibus (GEO) microarray database were integrated with machine learning techniques to identify key genes involved in both stones. Common targets then identified through Comparative Toxicogenomics Database (CTD) GeneCards. GMFA enrichment analysis performed shared biological pathways. Additionally, drug prediction molecular docking employed further investigate pharmacological relevance targets. Analysis NHANES confirmed a strong Weighted regression showed that (OR: 1.41; 95% CI 1.11–1.79; P < 0.001) bone loss 1.24; 1.08–1.43; significantly correlated an increased Three hub genes—WNT1, AKT1, TNF—were various analytical methods. revealed mTOR signaling pathway pathway. Molecular targets, demonstrating binding affinity drugs proteins involved, consistent findings. Bone associated Targeting may offer potential therapeutic approach for treating
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: April 28, 2025
Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by hepatic steatosis, inflammation and fibrosis, is becoming a global epidemic. However, the currently available effective clinical strategies remain limited. We conducted choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) induced MASH mouse model to explore effects of diphyllin on MASLD mice. employ targeted protein degradation technology applied for discovery compound/protein-protein interaction identify p65 as potential target protein. determine that diphyllin, natural arylnaphthalene lignan lactone, MASLD, evidenced inhibition lipid accumulation through promoting fatty acid oxidation in vivo vitro. To uncover underlying mechanisms, we design synthesis diphyllin-based protac Under deficiency, metabolism are blocked As an antagonist NRF2, interacts with p65, leading induction NRF2 transcriptional activity enhancement antioxidant capacity. When NFR2 inhibited, lowering abolished. Our study presents lead compound therapy but also offers novel approach elucidating mechanisms action products.
Language: Английский
Citations
0
Medicinal Research Reviews, Journal Year: 2025, Volume and Issue: unknown
Published: April 30, 2025
ABSTRACT Natural products have garnered significant attention due to their complex chemical structures and remarkable pharmacological activities. With inherent recognition capabilities for protein surfaces, natural serve as ideal candidates designing proteolysis‐targeting chimeras (PROTACs). The utilization of in PROTAC development offers distinct advantages, including rich diversity, multitarget activities, sustainable sourcing. This comprehensive review explores the vast potential harnessing research. Moreover, discusses application degradant technology, which involves utilizing product‐based compounds selectively degrade disease‐causing proteins, well implementation computer‐aided drug design (CADD) technology identifying suitable targets degradation within realm products. By power leveraging computational tools, PROTACs derived from revolutionize discovery provide innovative therapeutic interventions various diseases.
Language: Английский
Citations
0
Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3
Published: May 2, 2025
Language: Английский
Citations
0
European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 293, P. 117710 - 117710
Published: May 3, 2025
Language: Английский
Citations
0
Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(9), P. 7620 - 7634
Published: April 18, 2024
Meisoindigo (Mei) has long been recognized in chronic myeloid leukemia (CML) treatment. To elucidate its molecular target and mechanisms, we embarked on designing synthesizing a series of Mei-derived PROTACs. Through this endeavor, VHL-type PROTAC 9b was identified to be highly cytotoxic against SW620, SW480, K562 cells. Employing DiaPASEF-based quantitative proteomic analysis, combination with extensive validation assays, unveiled that potently selectively degraded ATM across SW620 SW480 cells ubiquitin–proteasome-dependent manner. 9b-induced selective degradation prompted DNA damage response cascades, thereby leading the cell cycle arrest apoptosis. This pioneering discovery renders advent for anti-cancer therapy. Notably, synergistically enhanced efficacy ATR inhibitor AZD6738 both vitro vivo. work establishes synthetic lethality-inducing properties inhibitors ATM-deficient context, providing new avenues innovative therapies colorectal cancer.
Language: Английский
Citations
3