产品说明书
XL019
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同义名 : | - |
| CAS号 : | 945755-56-6 | |
| 货号 : | A403201 | |
| 分子式 : | C25H28N6O2 | |
| 纯度 : | 99%+ | |
| 分子量 : | 444.529 | |
| MDL号 : | MFCD24386874 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 25 mg/mL(56.24 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
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| 描述 | The JAK/STAT3 pathway is activated by various cancer types, including glioma, and blockade of the pathway induces cell death in cancer cells. JAK2 is a member of the Janus family of cytoplasmic tyrosine kinases, with other members being JAK1, JAK3, and TYK. The normal function of JAK2 is to transmit signals following ligand binding of type I cytokine receptors, most notably the erythropoietin (EPO) and thrombopoietin receptors (MPL), the JAK2 V617F mutation results in loss of inhibition of its tyrosine kinase activity, and therefore its continuous activity leads to increased signaling through the JAK-signal transducer and activator of transcription (STAT) pathway[3]. XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2. It has been studied in a phase 1 clinical trial but was forced to terminate due to CNS side effects. KBV20C cancer cells were stimulated for 72 h with 5 nM vincristine, 5 μM XL019, 5 nM vincristine with 5 μM XL019. XL019 reduced cellular viability and increased apoptosis in vincristine-treated KBV20C cells. The result demonstrated that XL019 can sensitize drug-resistant KBV20C cancer cells to vincristine treatment by reducing the proliferation of vincristine-treated KBV20C cells. XL019 also induced early apoptosis of KBV20C cells in response to vincristine treatment via increasing G2 phase arrest. Moreover, G2 phase arrest and apoptosis of cells co-treated with vincristine and XL019 resulted from the up-regulation of phosphorylated retinoblastoma protein (pRb), p21, and the DNA-damage protein, phosphorylated H2A histone family, member X (pH2AX)[4]. | ||
| 作用机制 | The aniline substituted biarylpyrimidine core of XL019 can bind to the JAK2 binding site. | ||
| 临床研究 | |||||
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| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT00522574 | Myeloproliferative Disorders ... 展开 >> Myelofibrosis Polycythemia Vera Thrombocythemia, Essential 收起 << | Phase 1 | Terminated(Due to emerging saf... 展开 >>ety data) 收起 << | - | United States, California ... 展开 >> UCSF - Division of Hematology/Oncology San Francisco, California, United States, 94143 United States, Florida H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida, United States, 33612 United States, Massachusetts Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, New York Mt. Sinai School of Medicine New York, New York, United States, 10029 United States, Texas MD Anderson Cancer Center Houston, Texas, United States, 77030 收起 << |
| NCT00595829 | Polycythemia Vera | Phase 1 | Terminated | - | United States, California ... 展开 >> UCLA School of Medicine, Center for Health Sciences Los Angeles, California, United States, 90095 UCSF - Division of Hematology/Oncology San Francisco, California, United States, 94143 United States, Florida H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida, United States, 33612 United States, Michigan University of Michigan Health System Ann Arbor, Michigan, United States, 48109 United States, New York Weill Cornell Medical College New York, New York, United States, 10065 收起 << |
| 实验方案 | |||
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| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.25mL 0.45mL 0.22mL |
11.25mL 2.25mL 1.12mL |
22.50mL 4.50mL 2.25mL |
| 参考文献 |
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