亞盛醫藥-B(06855.HK)於美國癌症研究協會披露六項臨牀前研究結果
亞盛醫藥-B(06855.HK)公佈,在剛剛舉行的2022年美國癌症研究協會(AACR)年會上公佈六項最新臨牀前研究結果,包括公司細胞凋亡管線的兩個重要品種Bcl-2抑制劑lisaftoclax(APG-2575)、MDM2-p53抑制劑alrizomadlin(APG-115),FAK抑制劑APG-2449,EED抑制劑APG-5918,KRAS抑制劑APG-1842五個在研品種。
研究表明,APG-2575(lisaftoclax)聯合APG-115(alrizomadlin)可協同抑制攜帶BCL-2突變的RS4:11細胞的增殖及其在活體異種移植瘤模型中的生長。聯合靶向BCL-2和MDM2-p53細胞凋亡通路爲克服由BCL-2突變所導致的獲得性耐藥性提供一種有效的全新策略。
除細胞凋亡外,MDM2-p53抑制劑APG-115誘導caspase介導的GSDME陽性癌細胞焦亡。本研究首次揭示APG-115在表達GSDME的癌細胞中能誘導細胞凋亡和焦亡。GSDME依賴性焦亡是APG-115除抗腫瘤免疫外的一種未被認識的作用機制。
MDM2抑制劑APG-115與蛋白(酉每)體抑制劑聯合應用對TP53野生型的MM具有協同抗腫瘤作用。
APG-2449聯合palbociclib可通過誘導自噬和增強細胞衰老的方式協同抑制間皮瘤的腫瘤生長。臨牀前研究顯示,APG-2449聯合CDK4/6抑制劑可能對於間皮瘤具有治療潛力。
APG-5918的臨牀前表徵結果表明其具有強效的EED蛋白結合活性、體外抗增殖活性和體內抗腫瘤活性。APG-5918在體外和體內均表現出明確的靶點結合作用和靶點相關的抗腫瘤活性。APG-5918在KARPAS-422異種移植瘤小鼠中顯示出很強的PD/PK相關性。較MAK683這款正處於臨牀開發階段的EED抑制劑,APG-5918顯示相當或更優的生物化學特性以及體外和體內活性。
APG-1842是一個強效且具有高生物利用度和高選擇性的KRASG12C抑制劑。同時數據也爲APG-1842進一步應用於針對KRASG12C突變實體瘤患者的臨牀研究提供有力的臨牀前證據。
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