Druggable Protein-protein Interaction Assessment System (Dr. PIAS) is a database of druggable protein-protein interactions (PPIs) predicted by our support vector machine (SVM)-based method. Since the first publication of this database, Dr. PIAS has been updated to version 2.0. PPI data have been increased considerably, from 71,500 to 83,324 entries. As the new positive instances in our method, 4 PPIs and 10 tertiary structures have been added. This addition increases the prediction accuracy of our SVM classifier in comparison with the previous classifier, despite the number of added PPIs and structures is small. We have introduced the novel concept of 'similar positives' of druggable PPIs, which will help researchers discover small compounds that can inhibit predicted druggable PPIs. Dr. PIAS will aid the effective search for druggable PPIs from a mine of interactome data being rapidly accumulated. Dr. PIAS 2.0 is available at http://www.drpias.net.
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http://dx.doi.org/10.1093/database/bas034 | DOI Listing |
medRxiv
December 2024
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the causal biologically relevant gene is often challenging.
View Article and Find Full Text PDFExpert Opin Ther Pat
January 2025
Center for Therapeutics Discovery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Introduction: WDR5 is an epigenetic scaffolding protein that has attracted significant interest as an anti-cancer drug target, especially in MLL-rearranged leukemias. The most druggable 'WIN-site' on WDR5, which tethers WDR5 to chromatin, has been successfully targeted with multiple classes of exquisitely potent small-molecule protein-protein interaction inhibitors. Earlier progress has also been made on the development of WDR5 degraders and inhibitors at the 'WBM-site' on the opposite face of WDR5.
View Article and Find Full Text PDFACS Omega
December 2024
School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China.
V-domain immunoglobulin suppressor of T cell activation (VISTA), an inhibitory immune checkpoint present on both immune and tumor cells, has emerged as a highly promising target for cancer therapy due to its potential to overcome resistance encountered with existing immune checkpoint treatments. VSIG-3 is determined as an inhibitory ligand for VISTA, leading to the suppression of T cell proliferation. However, hotspots between VISTA/VSIG-3 protein-protein interaction remain ambiguous, mainly attributed to the lack of the structure of the VISTA/VSIG-3 complex.
View Article and Find Full Text PDFFront Immunol
December 2024
Centre for Targeted Protein Degradation, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
The Suppressor of Cytokine Signalling (SOCS) protein family play a critical role in cytokine signalling and regulation of the JAK/STAT pathway with functional consequences to the immune response. Members of this family are implicated in multiple different signalling cascades that drive autoimmune diseases and cancer, through their binding to phosphotyrosine modified proteins as well as ubiquitination activity as part of Cullin5 RING E3 ligases. Here we review the SOCS family members CISH and SOCS1-SOCS7, with a focus on their complex role in immunity.
View Article and Find Full Text PDFRedox Biol
December 2024
State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510632, China. Electronic address:
Osteosarcoma (OS) is the most prevalent malignant bone tumor in children and adolescents worldwide. Identification of novel therapeutic targets and development of targeted drugs are one of the most feasible strategies for OS treatment. Ferroptosis, a recently discovered mode of programmed cell death, has been implicated as a potential strategy for cancer therapy.
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