Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents

Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents

A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/...

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Veröffentlicht in:Computational and mathematical methods in medicine 2021-08, Vol.2021, p.1-9
Hauptverfasser: Li, Bing-Hui, Ge, Jun-Qi, Wang, Ya-Li, Wang, Li-Jun, Zhang, Qi, Bian, Cong
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container_title Computational and mathematical methods in medicine
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creator Li, Bing-Hui
Ge, Jun-Qi
Wang, Ya-Li
Wang, Li-Jun
Zhang, Qi
Bian, Cong
description A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/43250177, AG-690/37072075, AK-968/15254441, AO-022/43452814, and AF-399/25108021 showed promising MDM2 inhibition activities with Ki values of 9.5, 8.5, 23.4, 3.2, and 23.1 μM, respectively. Four compounds also showed antiproliferative activity, and compound AO-022/43452814 was the most potent hit with IC50 values of 19.35, 26.73, 12.63, and 24.14 μM against MCF7 (p53 +/+), MCF7 (p53 -/-), HCT116 (p53 +/+), and HCT116 (p53 -/-) cell lines, respectively. Compound AO-022/43452814 could be used as a scaffold for the development of anticancer agents targeting MDM2.
doi_str_mv 10.1155/2021/3195957
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title Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents
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