3α-Aminocholestane

SHP-1抑制剂(IC50=~2.5µM)；对SHP-1的选择性优于SHP-2和PTEN(IC50s=>20µM)；诱导患者来源的Ph+ALL细胞中SYK的过度活化；在50mg/kg剂量下，可减轻白血病负担并提高酪氨酸激酶抑制剂耐药患者来源的Ph+ALL小鼠异种移植模型中的存活率；以浓度依赖性方式降低OPM2细胞的细胞活力，并在≥12.5µM剂量下降低RPMI8226细胞的细胞活力；分别在高度增殖的OPM2细胞系或增殖性较低的RPMI8226细胞系中将细胞周期暂停在G0/G1或G2/M期；通过激活OPM2细胞中的caspase-3、caspase-9和PARP来诱导细胞凋亡，但在RPMI8226细胞中则不会。An inhibitor of SHP-1 (IC50 = ~2.5 µM); selective for SHP-1 over SHP-2 and PTEN (IC50s = >20 µM); induces hyperactivation of SYK in patient-derived Ph+ ALL cells; reduces leukemia burden and increases survival in a tyrosine kinase inhibitor-resistant patient-derived Ph+ ALL mouse xenograft model at 50 mg/kg; reduces cell viability of OPM2 cells in a concentration-dependent manner and of RPMI8226 cells at ≥12.5 µM; halts the cell cycle at the G0/G1 or G2/M stages in the highly proliferative OPM2 or less proliferative RPMI8226 cell lines, respectively; induces apoptosis via activation of caspase-3, caspase-9, and PARP in OPM2 cells but not in RPMI8226 cells.