{"title":"Computational drug repositioning for IL6 triggered JAK3 in rheumatoid arthritis using FDA database.","authors":"Kaushani Banerjee, Bavya Chandrasekar, Sruthy Sathish, Honglae Sohn, Thirumurthy Madhavan","doi":"10.1007/s11030-024-10958-x","DOIUrl":null,"url":null,"abstract":"<p><p>Rheumatoid Arthritis (RA) is a persistent autoimmune disease affecting approximately 0.5-1 percent of the world population. RA prevalence is higher in woman aged between 35 and 50 years than in age matched men, though this difference is less evident among elderly patients. The profound immune specific effects of disrupted JAK 3 (Janus kinase 3) signaling highlight the possibility of therapeutic targeting of JAK3 as a highly specific mode of immune system suppression. To address the above problem which is unendurable to patients and in the hope to cater some respite to such suffering we have targeted JAK 3 protein and JAK/STAT signaling pathway with compounds downloaded from FDA database, and performed screening of all available compounds docked against JAK3 protein. The difference between the target protein and other proteins of the same family was studied using cross docking and the compounds having higher binding affinity to JAK3 protein also showed more selectivity towards the particular protein. Density functional theory and molecular dynamics simulation study was done to study the compounds at their atomic level to know more about their drug likeliness. At the end of the study and based on our analysis we have come up with three FDA approved drugs that can be proposed as a treatment option for Rheumatoid Arthritis.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-10958-x","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
Abstract
Rheumatoid Arthritis (RA) is a persistent autoimmune disease affecting approximately 0.5-1 percent of the world population. RA prevalence is higher in woman aged between 35 and 50 years than in age matched men, though this difference is less evident among elderly patients. The profound immune specific effects of disrupted JAK 3 (Janus kinase 3) signaling highlight the possibility of therapeutic targeting of JAK3 as a highly specific mode of immune system suppression. To address the above problem which is unendurable to patients and in the hope to cater some respite to such suffering we have targeted JAK 3 protein and JAK/STAT signaling pathway with compounds downloaded from FDA database, and performed screening of all available compounds docked against JAK3 protein. The difference between the target protein and other proteins of the same family was studied using cross docking and the compounds having higher binding affinity to JAK3 protein also showed more selectivity towards the particular protein. Density functional theory and molecular dynamics simulation study was done to study the compounds at their atomic level to know more about their drug likeliness. At the end of the study and based on our analysis we have come up with three FDA approved drugs that can be proposed as a treatment option for Rheumatoid Arthritis.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;