| 名稱 | Spebrutinib |
| 描述 | Spebrutinib (LMK-435) is an orally bioavailable, selective inhibitor of Bruton's agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. |
| 細(xì)胞實(shí)驗(yàn) | A suspension of resting purified na?ve human B cells isolated by negative selection in RPMI is prepared at 0.4–0.5 × 106 cells/ml. Cells are mixed together with α-human IgM (final concentration of 5 μg/ml in each well) and vehicle (dimethyl sulfoxide) or AVL-292 (final concentrations of 0.01, 0.1, 1.0, 10.0, 100.0, or 1000 nM per well) and seeded in a 96-well plate. Cells are incubated for 56 hours in a humidified incubator maintained at 37°C and 5% CO2. 3H-Thymidine is added (final concentration of 1 μCi in each well) and cells are incubated overnight, harvested, and measured for 3H incorporation. Experiments are performed in triplicate.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Procedures for BTK OMNIA Assay: The Omnia continuous read assay is performed essentially as described by the vendor. The assay conditions are: 40 μM ATP (1X KMATP), 10 μM Y5-Sox, and 10 nM BTK enzyme. Briefly, a substrate mix containing 1.13X ATP and the Y5 Sox substrate is first prepared in 1X Omnia Kinase Reaction Buffer (KRB) consisting of 20 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EGTA, 5 mM?β-glycerophosphate, 5% glycerol, and 0.2 mM DTT. For IC50 measurements, 5 μL of enzyme are incubated with serially diluted (3-fold) compounds prepared in 50% DMSO in a Corning (#3574) 384-well, white, non-binding surface microtiter plate at 25°C for 30 min. Kinase reactions are started with the addition of 45 μL of the ATP/Y5 substrate mix and monitored at λex360/λem485 in a Synergy 4 plate reader for 60 minutes. Progress curves from each well are examined for linear reaction kinetics and fit statistics. Initial velocity from each reaction is determined from the slope of a plot of relative fluorescence units versus time and then plotted against inhibitor concentration to estimate IC50 using the Response, Variable Slope model in GraphPad Prism from GraphPad Software. |
| 體外活性 | 口服3-30 mg/kg AVL-292抑制膠原蛋白誘導(dǎo)的小鼠關(guān)節(jié)炎模型中的炎癥臨床癥狀,包括關(guān)節(jié)和爪腫脹以及感染爪的可見發(fā)紅的減少. |
| 體內(nèi)活性 | AVL-292通過抑制BTK的活性,進(jìn)一步抑制B細(xì)胞的增殖,EC50為3 nM。AVL-29對在Ramos細(xì)胞中的BTK產(chǎn)生抑制作用,EC50為8 nM,具有劑量依賴性,并且抑制了下游的BCR通路。 |
| 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 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 79 mg/mL (186.6 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Spebrutinib | inhibit | Bruton tyrosine kinase | CC 292 | Btk | AVL 292 | CC292 | Inhibitor | LMK 435 | AVL292 | LMK435 |
| 相關(guān)產(chǎn)品 | Pelitinib | Ponatinib | IBT6A | Vemurafenib | Bosutinib hydrate | TAK-901 | Staurosporine | Nintedanib | Dasatinib | (±)-Zanubrutinib | Ibrutinib | Orelabrutinib |
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