Comparative QSAR model generation using pyrazole derivatives for screening Janus kinase-1 inhibitors.,Chemical Biology & Drug Design

当前位置： X-MOL 学术 › Chem. Bio. Drug Des. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Comparative QSAR model generation using pyrazole derivatives for screening Janus kinase-1 inhibitors.
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2020-03-29 , DOI: 10.1111/cbdd.13667
Suvarna Sarithamol ₁ , Vadakkethil Lalithabhai Pushpa ₁ , Vasanthakumari Divya _{1,

2} , Kanthimathi Bahuleyan Manoj _{1,

3}

Affiliation

Asthma is a multitargeted disease. IL-4-JAK-STAT signaling pathway is a promising route for the effective control of the disease. JAK inhibition by small molecules could effectively block the IL-4 signaling pathway. It was established that JAK1 is responsive toward IL-4-mediated signaling process. In the present study, three-dimensional QSAR analyses on a set of pyrazole derivatives against JAK1 and JAK2 enzyme inhibition had been executed. Molecular docking studies were conducted with the target JAK1 using the pyrazole derivative compounds and found out potential intermolecular interactions operating among them. The binding energy of all the derivative compounds with the target JAK1 has calculated and found out their affinity toward the target system. These models have predicted the JAK1 inhibitory activity of some five JAK1 active drugs and 50 structurally similar compounds. These models can, thus, suggestively be recommended for virtual screening of JAK1-selective candidates as a lead for immunomodulatory diseases like asthma.

中文翻译：

使用吡唑衍生物生成比较 QSAR 模型以筛选 Janus 激酶-1 抑制剂。

哮喘是一种多靶点疾病。IL-4-JAK-STAT信号通路是有效控制疾病的有希望的途径。小分子对 JAK 的抑制可以有效阻断 IL-4 信号通路。已确定 JAK1 对 IL-4 介导的信号传导过程有反应。在本研究中，对一组对 JAK1 和 JAK2 酶抑制作用的吡唑衍生物进行了三维 QSAR 分析。使用吡唑衍生物化合物对目标 JAK1 进行了分子对接研究，并发现了它们之间潜在的分子间相互作用。所有衍生化合物与目标 JAK1 的结合能已经计算并发现它们对目标系统的亲和力。这些模型预测了约 5 种 JAK1 活性药物和 50 种结构相似化合物的 JAK1 抑制活性。因此，可以暗示性地推荐这些模型用于 JAK1 选择性候选者的虚拟筛选，作为免疫调节疾病（如哮喘）的先导。

更新日期：2020-03-29

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11