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 tu...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(T1/2)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.展开更多
基金Jiangsu Province policy guidance program(International Science and Technology Cooperation)-Overseas Joint laboratory Construction Project(Grant No.BZ2017044)Changzhou Science and Technology Support Plan(Social Development,Grant No.CE20185055)。
文摘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(T1/2)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.
