生物活性
Spebrutinib (AVL-292)是一个通过共价结合的，可以口头利用，并且具有高度选择性的BTK抑制剂，其IC50小于0.5 nM，展示了比其他被测激酶至少1400倍的选择性。Spebrutinib (AVL-292)在Ramos细胞中对BTK产生了剂量依赖性的抑制作用，其EC50为8 nM；并且抑制了下游的BCR通路。Spebrutinib (AVL-292)通过抑制BTK的活性，进一步的抑制了B细胞的增殖，其EC50为3 nM。
化学数据
| 分子量 | 423.44 |
| 分子式 | C22H22FN5O3 |
| CAS号 | 1202757-89-8 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 60 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | naive human B cells |
| 方法 | Immunoblot Analysis. Cells were incubated in serum-free RPMI media for 1–1.5 hours. Isolated human B cells were incubated with CC-292 at a final concentration of 0.001, 0.01, 0.1 and 1 μM. Ramos cells were incubated with 0.1 nM–3 μM CC-292. Cells were then incubated in the presence of compound for 1 hour at 37°C. Following incubation, cells were centrifuged and resuspended in 100 μl of serum-free RPMI and BCR was stimulated with addition of 5 μg/ml α-human IgM. Samples were centrifuged, washed in phosphate-buffered saline (PBS), and lysed in 100 μl of Cell Extraction Buffer [cat. no. FNN0011; Life Technologies (Invitrogen), Carlsbad, CA] plus 1:10 (v/v) PhosSTOP Phosphatase Inhibitor (Roche, Basel, Switzerland) and 1:10 (v/v) Complete Protease Inhibitor (cat. no. 11836145001; Roche). Antibodies used for immunoblot analysis include P-PLCγ2 [cat. no. 3872; Cell Signaling Technology, Beverly, MA (CST)], PLCγ2 (3871; CST), Syk (2712; CST), P-Syk (2710; CST), Btk (cat. no. 611116; BD Biosciences, Franklin Lakes, NJ), P-Btk (cat. no. 2207-1; Epitomics, Berlingame, CA), and Tubulin (cat. no. T6199; Sigma-Aldrich, St. Louis, MO). Membranes were scanned on a Li-Cor Odyssey scanner using infrared fluorescence detection (Li-Cor Biosciences, Lincoln, NB).. |
| 浓度 | 0.001, 0.01, 0.1 and 1 μM |
| 处理时间 | 1h |
| 动物实验 |
|---|
| 动物模型 | Collagen-Induced Arthritis Model |
| 配制 | not mentioned |
| 剂量 | 10,30,50 mg/kg |
| 给药处理 | oral |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3616 mL | 11.808 mL | 23.6161 mL |
| 5 mM | 0.4723 mL | 2.3616 mL | 4.7232 mL |
| 10 mM | 0.2362 mL | 1.1808 mL | 2.3616 mL |
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