空军军医大学学报2026，Vol.47Issue(6)：867-873,7.DOI:10.13276/j.issn.2097-1656.2026.06.012
一种新型Tankyrase抑制剂乙酰化衍生物改善孤独症小鼠社交障碍的作用
A novel acetylated derivative of Tankyrase inhibitor ameliorates social deficits in a mouse model of autism spectrum disorder
摘要
Abstract
Objective To investigate the effects of a novel esterified Tankyrase inhibitor(TNKI)on the social deficits in mice with autism spectrum disorder(ASD).Methods Esterification modification strategy was adopted to design and synthesize an acetylated TNKI(named as TNKI-Ac).Its inhibitory effects on Wnt signaling and glycolysis were evaluated using 293T cells and primary cortical neurons isolated from ASD mice(Shank3b-/-mice)through Western blotting,TOPflash assay,extracellular acidification rate,and intracellular lactate levels.The TNKI-Ac was administered to Shank3b-/-mice via tail vein injection,and its effects on social deficits were assessed by the three-chamber test,resident-intruder test and ultrasonic vocalization.Results Similar to the original TNKI,TNKI-Ac exhibited a dual inhibitory effect on Wnt signaling and glycolysis in both 293T cells and primary Shank3b-/-cortical neurons(P＜0.05).Superior to TNKI,tail vein injection of TNKI-Ac significantly ameliorated the social deficits(including social preference,social interaction and social communication)in Shank3b-/-mice(P＜0.05).Conclusion Esterification modification may improve the pharmacodynamic properties of TNKI to some extent.The acetylated derivative of TNKI can ameliorate the social deficits in ASD mice and may serve as a potential prodrug for further development.关键词
孤独症谱系障碍/社交障碍/Wnt信号/糖酵解/Tankyrase抑制剂/小分子化合物/酯化/Shank3b突变Key words
autism spectrum disorder/social deficits/Wnt signaling/glycolysis/Tankyrase inhibitor/small-molecule compound/esterification/Shank3b mutation分类
医药卫生引用本文复制引用
刘瀚泽,王娅蓉,王硕,于甜甜,王婧,王亚周,武胜昔,王梦梦,高枫..一种新型Tankyrase抑制剂乙酰化衍生物改善孤独症小鼠社交障碍的作用[J].空军军医大学学报,2026,47(6):867-873,7.基金项目
科技部科技创新-2030"脑科学与类脑研究"重大项目(2021ZD0201005) （2021ZD0201005）
陕西省重点研发计划项目(2025SF-YBXM-393) （2025SF-YBXM-393）
陕西省自然科学基础研究计划项目(2025JC-YBMS-1027) （2025JC-YBMS-1027）
