| 名稱 | Olverembatinib dimesylate |
| 描述 | Olverembatinib dimesylate (GZD824 Dimesylate) is a novel orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I). |
| 細胞實驗 | 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 | 每天20 mg/kg GZD824抑制表達的Bcr-AblWT和BCR-AblT315I的Ba/F3細胞的同種異體移植小鼠中腫瘤生長.每天5和10 mg/kg GZD824劑量依賴性地抑制了K562腫瘤異種移植物和KU812異種移植模型中腫瘤的生長,并且沒有死亡或體重減輕. |
| 體內(nèi)活性 | GZD824以濃度依賴性方式有效抑制白血病細胞中Bcr-Abl以及下游Crk1和STAT5的活化。與生化激酶抑制和蛋白質(zhì)結(jié)合親和力實驗結(jié)果高度相符,GZD824也強烈抑制表達Bcr-AblT315I突變體和其他14個與抗性有關(guān)的Bcr-Abl突變體的Ba/F3細胞的增殖。 |
| 存儲條件 | 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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| 關(guān)鍵字 | 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 |
| 相關(guān)產(chǎn)品 | Ponatinib | Pivanex | Imatinib | Bosutinib hydrate | KW-2449 | Masitinib | Nilotinib monohydrochloride monohydrate | Bosutinib | GNF-5 | Dasatinib | Imatinib Mesylate | Nilotinib |
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