FOXO3 is integral in regulating numerous genes involved in critical cellular processes such as apoptosis, oxidative damage protection, cell growth, and cancer. Consequently, modulating FOXO3 activity holds significant potential for applications in cancer treatment and cellular aging. A promising approach involves identifying small-molecule modulators that can either enhance or inhibit FOXO3's DNA-binding capability. This paper details a virtual screening protocol aimed at discovering such modulators. Utilizing the crystal structures of FOXO3 in both its free and DNA-bound forms, we pinpoint potential binding sites that may disrupt or facilitate the DNA-FOXO3 interaction. A comprehensive virtual screening of a small-molecule compound library is conducted using AutoDock Vina software. The highest-ranking hits for each site are carefully selected and analyzed to determine their binding modes. This protocol paves the way for identifying novel modulators of FOXO3, offering therapeutic avenues in cancer and aging-related research.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-1-0716-4217-7_11 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The interaction between meiosis-expressed gene 1 (MEIG1) and Parkin co-regulated gene (PACRG) is a critical determinant of spermiogenesis, the process by which round spermatids mature into functional spermatozoa. Disruption of the MEIG1-PACRG complex can impair sperm development, highlighting its potential as a therapeutic target for addressing male infertility or for the development of non-hormonal contraceptive methods. This study used virtual screening, molecular docking, and molecular dynamics (MD) simulations to identify small molecule inhibitors targeting the MEIG1-PACRG interface.
View Article and Find Full Text PDFVirtual screening assisted identification of a phytocompound as potent inhibitor against Candida lusitaniae; an in-silico study.
BMC Infect Dis
January 2025
Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia.
Candida lusitaniae is one of the fungal species which causes serious health illnesses including peritonitis, vaginitis and fungemia, among others. Several antifungal drugs have been designed to tackle its infections but their efficacy is still questionable due to their associated side effects. Hence, there is a need to design those drugs which possess comparatively higher degree of therapeutic potential.
View Article and Find Full Text PDFComputational modeling design of novel NMDAR agonist for the treatment of Schizophrenia.
Neurogenetics
January 2025
Department of Biochemistry, College of Medicine, University of Lagos, Lagos State, Nigeria.
Schizophrenia (SZ) is a complex, chronic mental disorder characterized by positive symptoms (such as delusions and hallucinations), negative symptoms (including anhedonia, alogia, avolition, and social withdrawal), and cognitive deficits (affecting attention, processing speed, verbal and visuospatial learning, problem-solving, working memory, and mental flexibility). Extensive animal and clinical studies have emphasized the NMDAR hypofunction hypothesis of SZ. Glycine plays a crucial role as an agonist of NMDAR, enhancing the receptor's affinity for glutamate and supporting normal synaptic function and plasticity, that is, signal transmission between neurons.
View Article and Find Full Text PDFDatabase Construction for the Virtual Screening of the Ruthenium-Catalyzed Hydrogenation of Ketones.
J Org Chem
January 2025
Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
During the recent development of machine-learning (ML) methods for organic synthesis, the value of "failed experiments" has increasingly been acknowledged. Accordingly, we have developed an exhaustive database comprising 300 entries of experimental data obtained by performing ruthenium-catalyzed hydrogenation reactions using 10 ketones as substrates and 30 phosphine ligands. After evaluating the predictive performance of ML models using the constructed database, we conducted a virtual screening of commercially available phosphine ligands.
View Article and Find Full Text PDFIdentification of 8-(2-methyl phenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a novel and selective TGFβ RII kinase inhibitor for breast cancer therapy.
Biochem Biophys Res Commun
January 2025
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. Electronic address:
Objective And Significance: Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!