丝裂原激活蛋白激酶7（MAPK7）是一种丝氨酸/苏氨酸蛋白激酶，属于MAPK家族，在细胞增殖、分化、基因转录、凋亡、代谢和细胞存活等多种细胞过程中发挥着至关重要的作用。 MAPK7 表达升高与人类多种侵袭性肿瘤的发生和进展相关，这强调了在治疗研究中靶向 MAPK7 通路的潜力。这一追求有望通过开发潜在的 MAPK7 抑制剂来推进抗癌药物的开发。为了寻找潜在的 MAPK7 抑制剂，我们利用 ZINC 数据库中的天然产物进行基于结构的虚拟筛选。首先，使用 Lipinski 五个标准规则来过滤约 90,000 种天然化合物的大型库，然后使用 ADMET 和泛分析干扰化合物 (PAINS) 过滤器。然后，根据分子对接确定的强结合亲和力来选择最佳命中。此外，还进行了相互作用分析，以找到能够精确结合 MAPK7 结合袋的有效且特异的化合物。因此，两种化合物 ZINC12296700 和 ZINC02123081 表现出显着的结合亲和力并表现出优异的药物样特性。 200ns 的全原子分子动力学模拟证实了 MAPK7-ZINC12296700 和 MAPK7-ZINC02123081 对接复合物的稳定性。根据分子力学泊松-玻尔兹曼表面积研究，两种配合物的结合亲和力相当大。总体而言，结果表明 ZINC12296700 和 ZINC02123081 可用作开发新型 MAPK7 抑制剂的有希望的先导化合物。由于这些化合物会干扰 MAPK7 的激酶活性，因此在经过必要的验证后可用于控制癌症中的细胞生长和增殖。© 2023 John Wiley

Mitogen-activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure-based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan-assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug-like properties. All-atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7-ZINC12296700 and MAPK7-ZINC02123081 docked complexes. According to the molecular mechanics Poisson-Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations.© 2023 John Wiley & Sons Ltd.