The innate immunity toll-like receptor 4 (TLR4) system is a receptor of paramount importance as a therapeutic target. Virtual screening following a "computer-aided drug repurposing" approach was applied to the discovery of novel TLR4 modulators with a non-lipopolysaccharide-like structure. We screened almost 29,000 approved drugs and drug-like molecules from commercial, public, and academia chemical libraries and, after biological assays, identified several compounds with TLR4 antagonist activity. Our computational protocol showed to be a robust approach for the identification of hits with drug-like scaffolds as possible inhibitors of the TLR4 innate immune pathways. Our collaborative work broadens the chemical diversity for inspiration of new classes of TLR4 modulators.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496124 | PMC |
| http://dx.doi.org/10.3390/biomedicines10092326 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
IFN alpha signaling drives hematopoietic stem cells malfunction under acute inflammation.
Int Immunopharmacol
January 2025
Department of Hematology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China. Electronic address:
Inflammation stimulation regulates the activity of hematopoietic stem cells (HSCs) through direct-sensing and cytokine-mediation. It is known that HSCs directly sense lipopolysaccharide (LPS), a classical infection-related inflammatory signal, via toll like receptor 4 (TLR4) and subsequently become active. However, the mechanism underlying the activity change of HSCs induced by LPS remains incompletely disclosed.
View Article and Find Full Text PDFPain in rheumatoid arthritis: Emerging role of high mobility group box 1 protein-HMGB1.
Life Sci
January 2025
Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Rheumatoid arthritis (RA) is a chronic inflammatory disease where pain, driven by both inflammatory and non-inflammatory processes, is a major concern for patients. This pain can persist even after joint inflammation subsides. High mobility group box-1 (HMGB1) is a non-histone-DNA binding protein located in the nucleus that plays a key role in processes such as DNA transcription, recombination, and replication.
View Article and Find Full Text PDFDesigning of an mRNA vaccine against high-risk human papillomavirus targeting the E6 and E7 oncoproteins exploiting immunoinformatics and dynamic simulation.
PLoS One
January 2025
Microbiology, Cancer and Bioinformatics Research Group, Noakhali Science and Technology University, Noakhali, Bangladesh.
Human papillomavirus 16 and human papillomavirus 18 have been associated with different life-threatening cancers, including cervical, lung, penal, vulval, vaginal, anal, and oropharyngeal cancers, while cervical cancer is the most prominent one. Several research studies have suggested that the oncoproteins E6 and E7 are the leading cause of cancers associated with the human papillomavirus infection. Therefore, we developed two mRNA vaccines (V1 and V2) targeting these oncoproteins.
View Article and Find Full Text PDFPost-translational modifications drive the effects of HMGB1 in alcohol-associated liver disease.
Hepatol Commun
November 2024
Department of Pathology, University of Illinois Chicago, Chicago, Illinois, USA.
Article Synopsis
- High-mobility group box-1 (HMGB1) levels rise and undergo post-translational modifications (PTMs) with alcohol consumption, potentially influencing the development of alcohol-associated liver disease (AALD).
- Researchers used a specific model of liver injury caused by alcohol to explore how manipulating HMGB1's expression and modifications in liver cells and immune cells impacts AALD.
- Their findings show that different forms of HMGB1 have contrasting effects: oxidized HMGB1 (O) worsens liver injury while acetylated HMGB1 (Ac) can protect against these harmful effects, highlighting the importance of targeting O HMGB1 in treating AALD.
Silencing FOXA1 suppresses inflammation caused by LPS and promotes osteogenic differentiation of periodontal ligament stem cells through the TLR4/MyD88/NF-κB pathway.
Biomol Biomed
December 2024
Department of Stomatology, Tianjin First Central Hospital, Nankai District, Tianjin, China.
Article Synopsis
- Human periodontal ligament stem cells (hPDLSCs) are essential for periodontal tissue regeneration, and the study investigates the role of FOXA1 in periodontal inflammation and osteogenic differentiation of these cells.
- Results indicate that FOXA1 expression increases in periodontal tissues from periodontitis patients and is further elevated by LPS treatment, leading to inflammatory responses and reduced osteogenic differentiation.
- Silencing FOXA1 can decrease inflammation by inhibiting the TLR4/MyD88/NF-κB pathway and enhance the osteogenic differentiation of hPDLSCs despite LPS-induced suppression.
Want 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!