| 名稱 | 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). |
| 細(xì)胞實驗 | 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) |
| 激酶實驗 | 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. |
| 體外活性 | Olverembatinib 強(qiáng)效抑制表達(dá)野生型 Bcr-Abl 的 Ba/F3 細(xì)胞增長，IC50 為 1.0 nM。與生化激酶抑制和緊密蛋白結(jié)合親和力高度一致，Olverembatinib 也強(qiáng)烈抑制表達(dá) Bcr-AblT315I 突變體及其他 14 種抗性相關(guān) Bcr-Abl 突變體的 Ba/F3 細(xì)胞增殖。此外，Olverembatinib 在濃度依賴的方式下有效抑制 K562 CML 細(xì)胞中 Bcr-Abl 及其下游 Crkl 和 STAT5 的活化。[1] |
| 存儲條件 | 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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| 關(guān)鍵字 | 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) |
| 相關(guān)產(chǎn)品 | Ponatinib | Pivanex | Imatinib | Bosutinib hydrate | KW-2449 | Masitinib | Vodobatinib | Nilotinib monohydrochloride monohydrate | Bosutinib | GNF-5 | Dasatinib | Nilotinib |
| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 臨床前化合物庫 | 臨床期小分子藥物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |