喹啉衍生化合物用於製備Tau蛋白病變類疾病之醫藥組成物上之用途

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

105114059

專利證號

I 587860

專利獲證名稱

喹啉衍生化合物用於製備Tau蛋白病變類疾病之醫藥組成物上之用途

專利所屬機關 (申請機關)

國立臺灣師範大學

獲證日期

2017/06/21

技術說明

阿茲海默氏症會造成持續性的認知能力下降和記憶力減退，是最常見的失智症。隨著人口老化增加，預估到2040年將增至8,000萬人。因此尋求有效遏止阿茲海默氏症進程之方法，乃當務之急。許多研究顯示，阿茲海默氏症的病理特徵Aβ類澱粉斑塊及過度磷酸化tau的神經纖維纏結，藉影響GSK-3β活性來驅動疾病。因此GSK-3β成為調停阿茲海默氏症的有效標的。本研究由Enamine資料庫的150萬個化合物中，經virtual screening後找到7種具有抑制GSK-3β活性潛力的化合物，並利用kinase assay確認這7種化合物均能抑制GSK3β的酵素活性。進一步將這7種化合物以表現∆K280 tauRD-DsRed之293/SH-SY5Y細胞作評估，發現其中VB-030 and VB-037可降低tau聚集，並可抑制tau的過度磷酸化，及在小鼠海馬迴初級培養中增進神經細胞neurite之生長。以上研究結果顯示VB-030 and VB-037有應用於臨床治療包括阿茲海默氏症的Tau蛋白病變疾病之潛能。 Alzheimer’s disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Lines of evidence have suggested that both hallmarks of AD, Aβ plaques and tau tangles, drive the pathogenesis of AD via modulation of the GSK-3β. Thus GSK-3β has emerged as a therapeutic target for intervention in AD. In this study, seven compounds with GSK-3β inhibition activity were first identified from 1.5 millions compounds in the Enamine database through virtual screening. All the identified compounds were further confirmed having GSK-3β inhibition activity by kinase assay. Among them, VB-030 and VB-037 were able to reduce the tau aggregation in ∆K280 tauRD-DsRed 293 cells. Both of them also significantly reduced tau phosoharylation in ∆K280 tauRD-DsRed SH-SY5Y cells and improved neurite outgrowth in mouse hippocampal primary culture under tau toxicity. These data suggest that VB-030 and VB-037 could have therapeutic potential for AD.

備註

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產學合作組

連絡電話

77341329

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