Background: ATP-binding cassette Super-family G member 2 protein is an active ATPbinding cassette transporter with the potential to combat cancer stem cells.

Objective: Due to the lack of potential ATP-binding cassette Super-family G member 2 inhibitors, we screened natural inhibitors, which could be a safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette Super-family G member 2 protein.

Methods: Three-dimensional structure of ATP-binding cassette Super-family G member 2 protein downloaded from the protein databank and chemical structures of 166 selected compounds of the training dataset were retrieved from PubChem. Drug-likeness and docking analysis was conducted to shortlist the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophorebased screening of Zbc library of ZINC database and Autodock Vina were utilized for molecular docking against the predicted active pocket of the target protein to evaluate the potential association of protein and ligands. The physiochemical properties of novel compounds were calculated by admetSAR respectively.

Results: Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates the least binding energy (-8.5) and the highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for a laboratory test to confirm its activity as an ATP-binding cassette Super-family G member 2 inhibitors.

Conclusion: Our computer-based study systematically selected natural lead compounds, which could be effective in inhibiting ATP-binding cassette Super-family G member 2 and may help reverse the effect of multidrug resistance to increase the effectiveness of chemotherapy in cancer treatment.

背景：ATP结合盒超家族G成员2蛋白是一种有效的ATP结合盒转运蛋白，具有与癌症干细胞抗争的潜力。

目的：由于缺乏潜在的ATP结合盒超家族G成员2抑制剂，我们筛选了天然抑制剂，它可能是通过阻断ATP结合盒超家族G成员2的调控来控制多药耐药性的安全来源。蛋白质。

方法：从蛋白质数据库中下载的ATP结合盒超家族G成员2蛋白质的三维结构以及训练数据集中166种选定化合物的化学结构。进行了药物相似性和对接分析，以筛选出药效基团产生的数据集。LigandScout 4.1.5用于基于药效团的ZINC数据库Zbc文库筛选和Autodock Vina用于与目标蛋白质的预测活性口袋进行分子对接，以评估蛋白质与配体的潜在关联。通过admetSAR分别计算了新化合物的理化性质。

结果：通过基于药效团的筛选，ZINC4098704（Rhein）被鉴定为先导化合物，具有最低的结合能（-8.5）和与目标蛋白质的最高结合亲和力，并显示出最佳的理化特性。强烈建议将该化合物用于实验室测试，以确认其作为ATP结合盒超家族G成员2抑制剂的活性。

结论：我们基于计算机的研究系统地选择了天然铅化合物，这些化合物可有效抑制ATP结合盒超家族G成员2，并可能有助于逆转多药耐药性的作用，从而提高化学疗法在癌症治疗中的有效性。