Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the off-targets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects.

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通过计算目标钓鱼系统分析奥西替尼潜在的脱靶活性。

奥希替尼是第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，用于治疗非小细胞肺癌。然而，其脱靶现象尚不清楚，对脱靶活动的系统分析仍有待进行。在这里，我们使用 PharmMapper 和 DRAR-CPI 识别了奥西替尼的脱靶，并使用 GeneMANIA 和 DAVID 服务器分析了相交的靶点。构建了药物-靶标-通路网络来可视化这些关联。结果显示，奥希替尼与 31 种脱靶、40 条京都基因和基因组百科全书通路以及 9 种疾病相关。网络分析表明，这些目标参与了癌症和其他生理过程。除EGFR外，分子对接分析显示7种蛋白，分别是Janus激酶3、过氧化物酶体增殖物激活受体α、肾素、丝裂原激活蛋白激酶、淋巴细胞特异性蛋白酪氨酸激酶、细胞分裂蛋白激酶2和原癌基因酪氨酸-蛋白激酶Src也可能是奥希替尼的潜在靶点。总之，奥希替尼预计将靶向多种蛋白质和途径，从而形成一个作用网络，通过该网络发挥系统的药理作用。