生物活性
SB-649868是一种口服有效的选择性 OX1 和 OX 2 受体拮抗剂,作用于 OX1 和 OX2 受体的pKi值分别为 9.4 和 9.5。雄性CD大鼠的药代动力学研究,以1 mg/kg,静脉注射和3 mg/kg po进行,表明对于在血浆中具有中等清除率的催眠药(Clp = 24 mL/min/kg),具有优异的药代动力学特征,半衰期短(<0.6 h),分布容积小(V ss = 1.1 l/kg),口服生物利用度极佳(F = 85%),血浆暴露量良好(Cmax)= 333 ng/mL)。SB-649868,在剂量为1,3和10 mg/kg的OX-A注射前3小时口服给药,引起剂量依赖性的OX-A诱导的梳理减少,如通过梳理的总时间和梳理次数所测量的(p < 0.01,以3和10 mg/kg po)。
化学数据
分子量 | 477.55 |
分子式 | C26H24FN3O3S |
CAS号 | 380899-24-1 |
纯度 | >98% |
溶解性(25°C) | DMSO 10 mM |
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 |
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细胞系 | Chinese Hamster Ovary (CHO) cells |
方法 | Chinese Hamster Ovary (CHO) cells stably transfected with human OX1 orexin receptor are cultured in Dulbecco's modified Eagle's medium F12 Ham, supplemented with 10% fetal bovine serum (FBS), 2 mg/mL glutamine, 600 μg/ml geneticin at 37 °C in an atmosphere of 95% air and 5% CO2. CHO cells stably transfected with human OX2 orexin receptor are cultured in alpha-MEM supplemented with 10% FBS, 100 units/mL penicillin G, 100 units/mL streptomycin and 400 μg/mL geneticin, at 37 °C in an atmosphere of 95% air and 5% CO2. Accumulation of IP1 is measured using IP-One HTRF terbium cryptate-based assay. OX1-CHO cells are seeded into white 384-well plate at the cell density of 1×104cells per well and cultured for 24 h in the presence of 5 mM sodium butyrate while OX2-CHO cells are seeded at the cell density of 4×104cells per well and cultured for 24 h in culture medium. After washings Hank's Balanced Salt Solution (HBSS) at room temperature containing 20 mM HEPES pH 7.4, 50 mM, LiCl and 0.1% Bovine Serum Albumin (BSA) cells are pre-incubated for 45 min with antagonist and then treated with agonist for 60 min at 37 °C. Detection reagents, IP1-d2 tracer and anti-IP1-cryptate are diluted in lysis buffer and added to the cells. Following 60 min incubation at room temperature, time-resolved fluorescence at 615 nm and 665 nm are measured with Envision Multilabel flash lamp reader with 100 flashes and 400 μs integration time. |
浓度 | final DMSO concentration not exceeding 0.5% for functional studies and 1% for binding studies |
处理时间 | 45 min |
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 |
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1 mM | 2.094 mL | 10.4701 mL | 20.9402 mL |
5 mM | 0.4188 mL | 2.094 mL | 4.188 mL |
10 mM | 0.2094 mL | 1.047 mL | 2.094 mL |