生物活性
Remibrutinib (LOU064) is a potent and highly selective covalent Inhibitor of Bruton's Tyrosine Kinase (BTK) with IC50 value of 1 nM. LOU064 (Remibrutinib) exhibits an exquisite kinase selectivity due to binding to an inactive conformation of BTK and has the potential for a best-in-class covalent BTK inhibitor for the treatment of autoimmune diseases. LOU064 (Remibrutinib) demonstrates potent in vivo target occupancy with an EC90 of 1.6 mg/kg and dose-dependent efficacy in rat collagen-induced arthritis.
化学数据
| 分子量 | 507.53 |
| 分子式 | C27H27F2N5O3 |
| CAS号 | 1787294-07-8 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO 100 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 | human monocytic cell line THP1, Human Blood B cell and Basophil |
| 方法 | The effects of LOU064 on signaling from the activating FcγR are assessed in the human monocytic cell line THP1 (ATCC, TIB-202). The THP1 cell line expresses the two activating FcγRs CD32a (FcγRII2) and CD64 (FcγRI) that signal through BTK. Briefly, 384 well culture plates are coated with pooled non-specific human IgG fraction. Serial compound dilutions are dispensed into the IgG-coated plates containing a small volume of tissue culture medium. Then THP1 cells that are pre-differentiated by vitamin D3 treatment for 5 days are added to each well. Twenty-four hours later the secretion of IL-8 in the supernatant of these culture wells is assessed by a homogenous immunoassay. |
| 浓度 | 3 nM, 10 nM, 30 nM, 100 nM, 300 nM |
| 处理时间 | 25 min, 50 min, 75 min, 100 min |
| 动物实验 |
|---|
| 动物模型 | Female Lewis rats, female C57BL/6 mice, male beagle dog |
| 配制 | - |
| 剂量 | 1 mg/kg, 3 mg/kg |
| 给药处理 | i.v. or p.o. administration |
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 | 1.9703 mL | 9.8516 mL | 19.7033 mL |
| 5 mM | 0.3941 mL | 1.9703 mL | 3.9407 mL |
| 10 mM | 0.197 mL | 0.9852 mL | 1.9703 mL |
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