生物活性

• 靶点

  Src IC50:0.8nM

  Abl IC50:1nM

  c-Kit IC50:79nM

• 描述The oncogenic tyrosine kinase Bcr-Abl plays a central role in the pathogenesis of chronic myelogenous leukemia, thus makes it as the therapy drug target. However, it is demonstrated that the mutations of Bcr-Abl kinase have been the most common mechanism of drug resistance, such as imatinib. Dasatinib Monohydrate is the monohydrate form of Dasatinib. Dasatinib is a potent Bcr-Abl inhibitor with IC50 values of 0.6nM, 0.8nM and 2.8nM for Abl, Src and Lyn, as well as IC50 values ranging in 0.1-1.8nM for different Abl mutations except the T315l mutation (measured by in vitro kinase assays). Consistent with the results from the kinase assays, Dasatinib showed more potent growth inhibition in Ba/F3 expressing various Abl mutations with a narrow range of low nanomoles, as well as the inhibition on Bcr-Abl tyrosine phosphorylation with IC50 values below 10nM，compared with imatinib. Dasatinib also showed inhibitory activity against Lck, yes and c-kit with IC50 values of 0.4nM, 0.5nM and 5nM, respectively, and possessed cellular antiproliferative activities on tumor cells of different origins, most potent to CML cell line K562 with IC50<1nM. Oral treatment with Dasatinib, at dose of both 5mg/kg and 50mg/kg on a 5 day on and 2 day off schedule for two cycles, demonstrated complete tumor regressions in a K562 xenograft model of CML.

• 动物研究
  剂量	Mice: 10 mg/kg[3] (i.v.); 5 mg/kg - 15 mg/kg[3] (p.o.) Rat: 10 mg/kg[3] (p.o.)
  给药途径	i.v., p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02883049	B Acute Lymphoblastic Leukemia... more >> Central Nervous System Leukemia Ph-Like Acute Lymphoblastic Leukemia Testicular Leukemia Untreated Adult Acute Lymphoblastic Leukemia Untreated Childhood Acute Lymphoblastic Leukemia Collapse <<	Phase 3	Recruiting	-	-
  NCT00390793	Acute Lymphoblastic Leukemia ... more >> BCR-ABL1 Fusion Protein Expression Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Philadelphia Chromosome Positive Recurrent Acute Lymphoblastic Leukemia t(9;22) Collapse <<	Phase 2	Active, not recruiting	August 31, 2020	United States, Texas ... more >> M D Anderson Cancer Center Houston, Texas, United States, 77030 Collapse <<
  NCT02143414	Acute Lymphoblastic Leukemia ... more >> B Acute Lymphoblastic Leukemia B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative Philadelphia Chromosome Positive Recurrent Adult Acute Lymphoblastic Leukemia Refractory Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Lymphoblastic Leukemia Collapse <<	Phase 2	Recruiting	-	-

• 更多
• 参考文献

• [1] Dargart JL, Fish K, et al. Dasatinib therapy results in decreased B cell proliferation, splenomegaly, and tumor growth in a murine model of lymphoma expressing Myc and Epstein-Barr virus LMP2A. Antiviral Res. 2012 Jul;95(1):49-56.

  [2] Shah NP, Lee FY, et al. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006 Jul 1;108(1):286-91.