成都先導(688222.SH):正在積極推進其靶標發現的工作,以充分論證TRIM21作為具備分子膠研究的價值
格隆匯9月22日丨成都先導(688222.SH)接受特定對象調研時表示,公司的TPD(靶向蛋白降解技術平台)主要在進行從DEL技術衍生的PROTAC和Molecular Glue(分子膠)的開發。目前,成都先導已經表達、純化並篩選了幾十種E3連接酶,從成都先導萬億級DNA編碼化合物庫中也鑑定得到了許多特異性的E3結合分子,尤其是一些沒有報道過任何結合分子的E3。這些分子也逐漸被開發成PROTAC且被證實對靶標蛋白能實現有效降解,比如基於DEL衍生的CRBN分子、BIRC7分子、TRIM21分子的PROTAC開發上。尤其是基於TRIM21分子開發的BRD4 PROTAC,與基於CRBN的PROTAC相比,實現了不同癌症細胞的降解差異性,為其組織特異性靶向降解的應用提供重要的依據;同時,在特定的癌症細胞中,其降解能力達到pM級別,優於同類CRBN PROTAC約8000倍。在細胞全蛋白組學質譜分析中,TRIM21對比CRBN的PROTAC,介導了差異性的激酶降解,提示TRIM21在未來TPD領域的應用中具有不同於CRBN的降解靶標空間。更重要的是,TRIM21配體具有潛在的分子膠功能,目前已經展示出對多種腫瘤細胞的抗增殖影響,我們正在積極推進其靶標發現的工作,以充分論證TRIM21作為具備分子膠研究的價值。
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