Cannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2

文献类型： 外文期刊

第一作者： Jin, Sha

作者： Jin, Sha;Lu, Yuyuan;Wang, Xiaohui;Jin, Sha;Lin, Cong;Wang, Yibo;Wang, Hongshuang;Wang, Xiaohui;Jin, Sha;Lu, Yuyuan;Wen, Xin;Xiao, Peng;Sun, Jinpeng;Li, Xiaodong;Peng, Yinghua;Wang, Xiaohui

作者机构：

期刊名称：JOURNAL OF MEDICINAL CHEMISTRY （ 影响因子：7.3； 五年影响因子：7.3 ）

ISSN： 0022-2623

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Opioid addiction is a chronically relapsing disorderthat causescritical public health problems. Currently, there is a lack of effectivedrug treatment. Herein, one cannabidiol derivative, CIAC001, was discovered as an effective agent for treating morphine-inducedaddiction. In vitro, CIAC001 exhibited significantlyimproved anti-neuroinflammatory activity with lower toxicity. In vivo, CIAC001 ameliorated the morphine-induced withdrawal reaction,behavioral sensitization, and conditional position preference by inhibitingmorphine-induced microglia activation and neuroinflammation. Targetfishing for CIAC001 by activity-based protein profilingled to the identification of pyruvate kinase M2 (PKM2) as the targetprotein. CIAC001 bound to the protein-proteininterface of the PKM2 dimer and promoted the tetramerization of PKM2.Moreover, CIAC001 exhibited an anti-neuroinflammatoryeffect by reversing the decrease of the PKM2 tetramer and inhibitingthe nuclear translocation of PKM2. In summary, this study identified CIAC001 as a lead compound in targeting PKM2 to treat morphine-inducedaddiction.

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