| 名称 | Olverembatinib dimesylate |
| 描述 | Olverembatinib dimesylate (GZD824 Dimesylate) is a novel orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I). |
| 细胞实验 | Cells in the logarithmic phase are plated in 96-well culture dishes. Twenty-four hours later, cells are treated with the corresponding compounds or vehicle control at the indicated concentration for 72 h. CCK-8 is added into the 96-well plates (10 μL/well) and incubated with the cells for 3 h. OD450 and OD650 are determined by a microplate reader. Absorbance rate (A) for each well is calculated as OD450 – OD650. The cell viability rate for each well is calculated as V% = (As – Ac)/(Ab – Ac) × 100%, and the data were further analyzed using Graphpad Prism5. The data are the mean value of the three experiments. As is the absorbance rate of the test compound well, Ac is the absorbance rate of the well without either cell or test compound, and Ab is the absorbance rate of the well with cell and vehicle control.(Only for Reference) |
| 激酶实验 | FRET-Based Z′-Lyte Assay Detecting Peptide Substrate Phosphorylation: The kinases ABL1, ABL1(E255K), ABL1 (G250E), ABL1(T315I), and ABL1(Y253F) are P3049, PV3864, PV3865, PV3866, and PV3863 are full-length human recombinant protein expressed in insect cells and histidine-tagged. Inhibition activities of inhibitors against Abl1 and its mutants are performed in 384-well plates using the FRET-based Z′-Lyte assay system. Briefly, the kinase substrate is diluted into 5 μL of kinase reaction buffer; and the kinase is added. Compounds (10 nL) with indicated concentrations are then delivered to the reaction by using Echo liquid handler, and the mixture is incubated for 30 min at room temperature. Then 5 μL of 2X ATP solution is added to initiate the reaction, and the mixture is further incubated for 2 h at room temperature. The resulting reactions contains 10 μM (for wild-type Abl1, and mutants Y253F, Q252H, M351T, and H396P) or 5 μM (for mutants E255K, G250E, T315I) of ATP, 2 μM of Tyr2 Peptide substrate in 50 mM HEPES (PH 7.5), 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA, 0.0247 μg/mL Abl1, and inhibitors as appropriate. Then, 5 μL of development reagent is added, and the mixture is incubated for 2 h at room temperature before 5 μL of stop solution is added. Fluorescence signal ratio of 445 nm (Coumarin)/520 nm (fluorescin) is examined on an EnVision Multilabel Reader. The data are analyzed using Graphpad Prism5. The data are the mean value of three experiments. |
| 体外活性 | 每天20 mg/kg GZD824抑制表达的Bcr-AblWT和BCR-AblT315I的Ba/F3细胞的同种异体移植小鼠中肿瘤生长.每天5和10 mg/kg GZD824剂量依赖性地抑制了K562肿瘤异种移植物和KU812异种移植模型中肿瘤的生长,并且没有死亡或体重减轻. |
| 体内活性 | GZD824以浓度依赖性方式有效抑制白血病细胞中Bcr-Abl以及下游Crk1和STAT5的活化。与生化激酶抑制和蛋白质结合亲和力实验结果高度相符,GZD824也强烈抑制表达Bcr-AblT315I突变体和其他14个与抗性有关的Bcr-Abl突变体的Ba/F3细胞的增殖。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : 92 mg/mL (126.9 mM)
DMSO : 93 mg/mL (128.3 mM)
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| 关键字 | region-Abelson | phosphorylated | imatinib | Olverembatinib dimesylate | inhibit | linase | Inhibitor | HQP-1351 | nonphosphorylated | breakpoint | resistance | GZD-824 Dimesylate | HQP 1351 | HQP1351 dimesylate | Olverembatinib Dimesylate | GZD 824 Dimesylate | GZD-824 | GZD824 | Bcr-Abl | Bcr-Abl(T315I) | GZD 824 | cluster | Olverembatinib |
| 相关产品 | Ponatinib | Pivanex | Imatinib | Bosutinib hydrate | KW-2449 | Masitinib | Nilotinib monohydrochloride monohydrate | Bosutinib | GNF-5 | Dasatinib | Imatinib Mesylate | Nilotinib |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | 激酶抑制剂库 | 神经退行性疾病化合物库 | 药物功能重定位化合物库 | 酪氨酸激酶分子库 | 抗癌临床化合物库 | 抗癌药物库 |
