| 名称 | Olverembatinib |
| 描述 | Olverembatinib (GZD 824) is an orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT, IC50: 0.34 nM) and Bcr-Abl(T315I, IC50: 0.68 nM). |
| 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 | Olverembatinib 强效抑制表达野生型 Bcr-Abl 的 Ba/F3 细胞增长，IC50 为 1.0 nM。与生化激酶抑制和紧密蛋白结合亲和力高度一致，Olverembatinib 也强烈抑制表达 Bcr-AblT315I 突变体及其他 14 种抗性相关 Bcr-Abl 突变体的 Ba/F3 细胞增殖。此外，Olverembatinib 在浓度依赖的方式下有效抑制 K562 CML 细胞中 Bcr-Abl 及其下游 Crkl 和 STAT5 的活化。[1] |
| 存储条件 | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 100 mg/mL (187.77 mM), Sonication is recommended.
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| 关键字 | resistance | region-Abelson | phosphorylated | Olverembatinib | nonphosphorylated | linase | Inhibitor | inhibit | imatinib | HQP-1351 | HQP1351 | HQP 1351 | GZD-824 | GZD824 | cluster | breakpoint | Bcr-Abl(T315I) | Bcr-Abl | BcrAbl | Abl (E254K) |
| 相关产品 | Ponatinib | Pivanex | Imatinib | Bosutinib hydrate | KW-2449 | Masitinib | Vodobatinib | Nilotinib monohydrochloride monohydrate | Bosutinib | GNF-5 | Dasatinib | 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 | 临床前化合物库 | 临床期小分子药物库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |