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QHRD107是细胞周期蛋白依赖性激酶(CDK)9的特异性抑制剂.体外对白血病细胞增殖具有高度抑制作用,在急性髓系白血病异种移植模型体内显著抑制肿瘤细胞生长,并能显著延长小鼠寿命.Molm-13异种移植模型单次灌胃给予QHRD107后,QHRD107迅速被吸收并靶向性分布至肿瘤组织,肿瘤半衰期(T1/2)较血浆延长3倍.伴随着肿瘤组织中高浓度QHRD107的暴露,抗凋亡蛋白Mcl-1 mRNA快速下调,Ki-67细胞表达降低证明肿瘤细胞凋亡.研究结果表明治疗剂量下的QHRD107对AML细胞具有显著的抗肿瘤活性.“,”QHRD107 is a specific inhibitor of cyclin-dependent kinase 9(CDK9).It is a highly potent antiproliferative agent against leukemia cells in vitro.Oral administration of QHRD107 to mice bearing acute myeloid leukemia tumors markedly inhibited tumor growth.In Molm-13 orthotopic model,QHRD107 resulted in remarkable prolongation of animal life span.After single oral administration of QHRD107 to Molm-13 xenograft model,QHRD107 was quickly absorbed and distributed to tumor with high concentration within 1 h.Tumor half-life time(T112)was three times longer compared with that of plasma.Under the high exposure of QHRD107 in tumor tissue,fast down-regulation of anti-apoptotic protein Mcl-1 mRNA was noted.Reduction of Ki-67 staining in tumor tissue further demonstrated the apoptosis of tumor cells.Therefore,the results provided evidence that QHRD107 at therapeutic dose had significant antitumor activity against AML cell lines.