利用 FDA 数据库计算类风湿性关节炎中 IL6 触发 JAK3 的药物重新定位。

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED
Kaushani Banerjee, Bavya Chandrasekar, Sruthy Sathish, Honglae Sohn, Thirumurthy Madhavan
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引用次数: 0

摘要

类风湿性关节炎(RA)是一种顽固的自身免疫性疾病,约占世界总人口的 0.5%-1%。35至50岁女性的类风湿关节炎发病率高于年龄匹配的男性,但这一差异在老年患者中并不明显。JAK 3(Janus 激酶 3)信号传导紊乱会产生深远的免疫特异性影响,这凸显了以 JAK3 为治疗靶点作为高度特异性免疫系统抑制模式的可能性。为了解决上述令患者难以忍受的问题,并希望为这种痛苦提供一些喘息的机会,我们从 FDA 数据库中下载了针对 JAK 3 蛋白和 JAK/STAT 信号通路的化合物,并对所有与 JAK3 蛋白对接的可用化合物进行了筛选。利用交叉对接法研究了目标蛋白与同族其他蛋白之间的差异,结果表明,与 JAK3 蛋白结合亲和力较高的化合物对该特定蛋白具有更高的选择性。密度泛函理论和分子动力学模拟研究从原子水平对化合物进行了研究,以进一步了解它们的药物相容性。研究结束后,根据我们的分析,我们得出了三种经 FDA 批准的药物,可作为类风湿关节炎的治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Computational drug repositioning for IL6 triggered JAK3 in rheumatoid arthritis using FDA database.

Computational drug repositioning for IL6 triggered JAK3 in rheumatoid arthritis using FDA database.

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.

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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
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;
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