靶点：Bcl-xL 通路：Apoptosis 背景说明：A-1331852是一种有效的、选择性的BCL-XL抑制剂。 生物活性：A-1331852 is an orally available BCL-XL selective inhibitor with a Ki of less than 10 pM.[1] In Vitro：A-1331852 selectively disrupts BCL-XL–BIM complexes and induces the hallmarks of apoptosis in BCL-XL–dependent Molt-4 cells with IC50s in the low nanomolar range but does not affect MEF cells lacking BAK or BAX. In CellTiter-Glo cell viability assay，A-1331852 inhibits NCI-H847，NCI-H1417，SET-2，HEL，OCI-M2 with EC50 values of 3，7，80，120 and 100 nM[1]. In Vivo：A-1331852 demonstrates antitumor efficacy in the Molt-4 xenograft model，inducing tumor regressions as a single agent. Additionally，A-1331852 combines with venetoclax to recapitulate the efficacy of navitoclax in the NCI-H1963.FP5 xenograft model of SCLC. A-1331852 significantly inhibits tumor growth in seven subcutaneous xenograft models of solid tumors，including breast cancer，NSCLC，and ovarian cancer[1]. 细胞实验：SCLC and AML cell lines are incubated with increasing concentrations of navitoclax，venetoclax，or A-1155463 for 48 hours before assessing cell viability. Cell killing EC50 values are calculated[1]. 动物实验：Mice: The growth inhibition of established tumors in SCID-bg mice is studied. A-1331852 is administered orally daily for 14 days at 25 mg/kg and RP-56976 is administered intravenously at 7.5 mg/kg. The change of tumor volume is monitored daily[1]. 数据来源文献：[1]. Leverson JD， et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med. 2015 Mar 18;7(279):279ra40.
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