Future medicinal chemistry · 2025
Protein profiling uncovers IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Myrsing Efficiency, Mouli H M Chandra, Nikhil Pallaprolu, Deepali, Sahu Abhishek, Jana Anupam, Ramalingam P
Аннотация
AIM: This study investigates the anti-proliferative potential and possible molecular mechanisms of 3-(2-furoyl)-indole derivatives against HepG2.
METHOD: Identified hit compounds (4a, 4b, 4c) using MTT screening, were further investigated for their efficacy and mechanism of action through FACS studies, in-silico molecular docking, molecular dynamics (MD) simulations, and label-free quantitative proteome and ADMET prediction.
RESULTS: Lead compound 4a, showed IC50 of 27 µM against HepG2 cells and a binding score of -8.077 kcal/mol against IGF-1 R (PDB ID: 5XFS) and formed a stable complex 100 ns. Proteomic study revealed significant downregulation of the IGF-1 R downstream signaling molecules and showed minimal toxicity and favorable drug-like properties.
CONCLUSION: These findings suggest that 4a is a promising IGF-1 R inhibitor and potential drug candidate against drug resistance hepatocellular carcinoma (HCC).
METHOD: Identified hit compounds (4a, 4b, 4c) using MTT screening, were further investigated for their efficacy and mechanism of action through FACS studies, in-silico molecular docking, molecular dynamics (MD) simulations, and label-free quantitative proteome and ADMET prediction.
RESULTS: Lead compound 4a, showed IC50 of 27 µM against HepG2 cells and a binding score of -8.077 kcal/mol against IGF-1 R (PDB ID: 5XFS) and formed a stable complex 100 ns. Proteomic study revealed significant downregulation of the IGF-1 R downstream signaling molecules and showed minimal toxicity and favorable drug-like properties.
CONCLUSION: These findings suggest that 4a is a promising IGF-1 R inhibitor and potential drug candidate against drug resistance hepatocellular carcinoma (HCC).
Предметные рубрики MeSH
HumansLiver NeoplasmsCarcinoma, HepatocellularReceptor, IGF Type 1Hep G2 CellsIndolesAntineoplastic AgentsMolecular Docking SimulationCell ProliferationDrug Screening Assays, AntitumorMolecular Dynamics SimulationProtein Kinase InhibitorsStructure-Activity RelationshipMolecular StructureDose-Response Relationship, Drug