Jumonji-C (JmjC) domain-containing 7 (JMJD7), which is a 2-oxoglutarate (2OG)-dependent oxygenase, has been demonstrated to play an important role in the occurrence and development of a number of diseases, particularly cancer. Discovery of JMJD7 inhibitors is thus of great importance. Herein consensus docking/scoring strategy and bioactivity evaluation were used to identify JMJD7 inhibitors from various chemical databases. Seven active compounds were retrieved. The most potent compound, Cpd-3, showed an IC₅₀ value of 6.62 μM against JMJD7. Further biophysical assays confirmed that Cpd-3 could efficiently bind to JMJD7 in vitro. Flexible docking was used to predict the binding mode of Cpd-3 with JMJD7. In a cellular assay, Cpd-3 displayed good inhibitory activity against cancer cell lines expressing a high level of JMJD7. As far as we know, Cpd-3 is the first JMJD7 inhibitor reported so far. Overall, this study established a good starting point for drug discovery targeting JMJD7.

Jumonji-C (JmjC) 域含 7 (JMJD7) 是一种 2-酮戊二酸 (2OG) 依赖性加氧酶，已被证明在许多疾病，尤其是癌症的发生和发展中起重要作用。因此，发现 JMJD7 抑制剂非常重要。在此共识对接/评分策略和生物活性评估用于从各种化学数据库中识别 JMJD7 抑制剂。回收了七种活性化合物。最有效的化合物Cpd-3对 JMJD7的 IC ₅₀值为 6.62 μM。进一步的生物物理分析证实，Cpd-3可以在体外有效结合 JMJD7 。灵活对接用于预测Cpd-3的结合模式与 JMJD7。在细胞试验中，Cpd-3对表达高水平 JMJD7 的癌细胞系显示出良好的抑制活性。据我们所知，Cpd-3是迄今为止报道的第一个JMJD7抑制剂。总体而言，这项研究为靶向 JMJD7 的药物发现奠定了良好的起点。