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歌禮制藥-B(01672.HK):3CLpro抑制劑ASC11有望成為治療新冠肺炎的有效藥物
格隆匯 04-19 16:46

格隆匯4月19日丨歌禮制藥-B(01672.HK)宣佈,其口服小分子候選藥物ASC11(3CLpro抑制劑)有望成為治療新冠肺炎的有效藥物。

抗新冠病毒細胞實驗顯示,ASC11的抗病毒活性(EC90)為奈瑪特韋的31倍(155/5),S-217622的120倍(600/5),PBI-0451的16倍(78/5)以及EDP-235的7倍(33/5)。重要的是,ASC11對新冠病毒不同的變異株均保持活性。

ASC11是利用包括分子模擬對接等專有技術自主研發的、靶點為3CLpro的口服小分子候選藥物,擁有全球知識產權。

分子模擬對接技術顯示,與奈瑪特韋相比,ASC11與3CLpro的穀氨酸166形成的氫鍵相互作用更強;與3CLpro的其它關鍵氨基酸形成新的氫鍵相互作用;與3CLpro的疏水性空腔P4結合更好,導致ASC11的的抗病毒活性(EC90)遠高於奈瑪特韋。

分子模擬對接技術顯示,與S-217622相比,ASC11和3CLpro的結合方式不同,導致ASC11的的抗病毒活性(EC90)遠高於S-217622。

在VeroE6細胞中,ASC11的安全窗(細胞毒性對比抗病毒活性)超過10,000倍。

結合其它臨牀前數據,包括Caco-2細胞(人結直腸腺癌細胞)滲透性、體外代謝、微粒體代謝穩定性和動物藥代動力學等研究,ASC11有望成為治療新冠肺炎的同類最佳藥物。

歌禮預計在2022年下半年提交ASC11臨牀試驗申請,2022年底前完成在健康受試者中的I期臨牀試驗。

公司第二款完全自主研發的、擁有全球知識產權的3CLpro候選藥物在VeroE6細胞中顯示出與ASC11一致的抗病毒活性和安全窗。

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