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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