中文摘要
本申请项目将首次对小分子Wnt信号通路激动剂抗白癜风活性进行研究。促进黑素细胞发育、增殖及黑色素合成是目前白癜风治疗领域的重要研究方向。已有研究表明Wnt信号通路的激活可以显著促进黑素细胞发育、增殖及黑色素合成,因此,小分子Wnt信号通路激动剂可望成为抗白癜风新型药物。菲啶化合物是近年才被申请人所在团队与中国科学院上海生命科学院合作发现的首个靶向Axin的Wnt信号通路激动剂,尚未见其抗白癜风的相关研究报道。本申请将首次对其抗白癜风活性进行研究,包括菲啶类Wnt信号通路激动剂促进成黑素细胞增殖及黑色素合成活性及基于靶蛋白Axin的作用机制研究;新型菲啶类Wnt信号通路激动剂活性定向设计;菲啶类化合物抗白癜风动物实验。通过上述研究,探索菲啶类化合物抗白癜风的作用机制与作用靶点,靶向Axin抗白癜风药物的可能性和可行性及相关动物试验。可望为白癜风新型治疗药物创制提供新策略与新思路。
英文摘要
In this study, the evaluation on anti-vitiligo activities of small-molecule Wnt agonists would be conducted for first time. Promoting the proliferation of melanocytes and synthesis of melanin would improve the symptoms of vitiligo and previous research has shown that activation of Wnt signaling pathway would promote the proliferation of melanocytes and synthesis of melanin. Hence, small-molecule Wnt agonists are expected to be new anti-vitiligo agents. Phenanthridine Wnt agonists are newly discovered by applicant and cooperation partners and these new Wnt agonists have not been evaluated their anti- vitiligo activities yet. In this research project, the anti-vitiligo activities of small-molecule Wnt agonists would be studied for the first time involving the promoting activities of phenanthridine Wnt agonists on the proliferation of melanocytes and synthesis of melanin and the mode of actions which targeting Axin protein; the design and synthesis of new potent phenanthridine Wnt agonists; the anti-vitiligo animal experiments of phenanthridine compounds. By the above-mentioned researches, Some new strategies and innovations would be made in developing new anti-vitiligo agents.
