Study on the bioactivity against hematologic malignancies and theoretical binding mechanism of a novel PI3K inhibitor JN-65

KE Ke; JIANG Wenli; WANG Yu; ZHU Jingyu; JIN Jian

doi:10.11665/j.issn.1000-5048.20190405

Journal of China Pharmaceutical University > 2019 > 50(4): 410-416. > DOI: 10.11665/j.issn.1000-5048.20190405

KE Ke, JIANG Wenli, WANG Yu, ZHU Jingyu, JIN Jian. Study on the bioactivity against hematologic malignancies and theoretical binding mechanism of a novel PI3K inhibitor JN-65[J]. Journal of China Pharmaceutical University, 2019, 50(4): 410-416. DOI: 10.11665/j.issn.1000-5048.20190405

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Study on the bioactivity against hematologic malignancies and theoretical binding mechanism of a novel PI3K inhibitor JN-65

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Abstract

The PI3K signaling pathway is frequently over-expressed in a variety of hematologic malignancies, so the development of PI3K inhibitors for the treatment of hematologic malignancies has broad application prospects. In this study, a novel PI3K inhibitor, JN-65, was identified through the investigation effects in the inhibition to hematologic malignancies. By MTT assays, JN-65 was found to effectively suppress the proliferation of hematologic malignancies, especially leukemia cell lines. The cell-free enzymatic studies demonstrated that JN-65 cloud inhibit PI3K and specifically inhibited PI3Kγ at low micromolar concentrations. Western blot confirmed that JN-65 could effectively inhibit the PI3K/Akt signaling pathway and the flow cytometry assays verified that JN-65 could induce the apoptosis of tumor cells through the suppression of PI3K signaling pathway. Finally, the molecular docking simulation method was used to explore the interaction between JN-65 and PI3K, and the inhibition mechanism of PI3K was revealed at the molecular level. In general, JN-65 would be a potential PI3K inhibitor for the treatment of hematologic malignancies.
- PI3K inhibitor,
- JN-65,
- hematologic malignancies,
- leukemia,
- molecular docking

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Study on the bioactivity against hematologic malignancies and theoretical binding mechanism of a novel PI3K inhibitor JN-65

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