Banerjee Kaushani, Chandrasekar Bavya, Sathish Sruthy, Sohn Honglae, Madhavan Thirumurthy
Computational Biology Lab, Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, SRM Nagar, Potheri, Kattankulathur, Chengalpattu District, Tamil Nadu, 603203, India.
Department of Chemistry and Department of Carbon Materials, Chosun University, Gwangju, South Korea.
Mol Divers. 2025 Jun;29(3):2049-2061. doi: 10.1007/s11030-024-10958-x. Epub 2024 Aug 14.
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.
类风湿性关节炎(RA)是一种持续性自身免疫性疾病,影响着全球约0.5%-1%的人口。35至50岁女性的RA患病率高于年龄匹配的男性,不过这种差异在老年患者中不太明显。JAK 3(Janus激酶3)信号通路紊乱所产生的深刻免疫特异性效应,凸显了将JAK3作为免疫系统抑制的一种高度特异性模式进行靶向治疗的可能性。为了解决上述患者难以忍受的问题,并希望能为这种痛苦提供一些缓解,我们利用从美国食品药品监督管理局(FDA)数据库下载的化合物,靶向JAK 3蛋白和JAK/STAT信号通路,并对所有与JAK3蛋白对接的可用化合物进行筛选。通过交叉对接研究了目标蛋白与同一家族其他蛋白之间的差异,与JAK3蛋白具有更高结合亲和力的化合物对该特定蛋白也表现出更高的选择性。进行了密度泛函理论和分子动力学模拟研究,以在原子水平上研究这些化合物,从而更深入了解它们的药物适用性。在研究结束时,基于我们的分析,我们提出了三种FDA批准的药物,可作为类风湿性关节炎的治疗选择。
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