| 名稱(chēng) | Danusertib |
| 描述 | Danusertib (PHA-739358) is a small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Danusertib binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed. |
| 細(xì)胞實(shí)驗(yàn) | For short-term expansion assays, 1 × 103 CD34+ cells are plated in triplicates in 96-well plates containing 100 μL of serum-free medium per well supplemented with human stem-cell factor (100 ng/mL), human Flt-3 Ligand (100 ng/mL), human thrombopoietin (50 ng/mL), human interleukin-3 and -6 (IL-3 and IL-6, respectively, both 20 ng/mL), and granulocyte colony-stimulating factor (20 ng/mL) along with Danusertib at the indicated concentrations. After 5 days, an additional 100 μL of cytokine and Danusertib containing medium are added. Cell numbers within each individual well are estimated on days 3, 6, and 9 or on days 3, 6, and 12 for healthy donor samples. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Biochemical kinase Assays: The Km values for ATP and the specific substrate are initially determined, and each assay is then run at optimized ATP (2Km) and substrate (5Km) concentrations. This setting enabled direct comparison of IC50 values of Danusertib across the applied kinase selectivity screening panel for the evaluation of the selectivity profile. |
| 體外活性 | Danusertib顯著抑制K562細(xì)胞的增殖,并在10天的治療期間抑制腫瘤的生長(zhǎng).給予HL-60異種移植大鼠25 mg/kg Danusertib（b.d.i.v.）導(dǎo)致75％的腫瘤生長(zhǎng)被抑制,并且在一只動(dòng)物中完全消退. |
| 體內(nèi)活性 | 在細(xì)胞測(cè)定中,在用Danusertib處理野生型和p53缺陷型MEF后,野生型細(xì)胞在有絲分裂（4N）中停滯,持續(xù)48小時(shí),而p53缺陷細(xì)胞不會(huì)在4N DNA階段停滯,持續(xù)有絲分裂,DNA變?yōu)?8N。Danusertib處理導(dǎo)致p53蛋白水平的上升和p21蛋白的增多,已知p53在轉(zhuǎn)錄水平上調(diào)節(jié)p21蛋白。Danusertib抑制其他激酶如FGFR1,Abl,Ret和Trka的活性,IC50分別為47 nM,25 nM,31 nM和31 nM。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 88 mg/mL (185.4 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | inhibit | PHA 739358 | Autophagy | Danusertib | PHA739358 | Inhibitor | Aurora Kinase |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Ferulic Acid | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 抗癌活性化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 激酶抑制劑庫(kù) | 膜蛋白靶向化合物庫(kù) | 酪氨酸激酶分子庫(kù) | 藥物功能重定位化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |