RO0270608
(Synonyms: (S)-2-(2-氯-6-甲基苯甲酰氨基)-3-(4-(2,6-二氯苯甲酰氨基)苯基)丙酸) 目录号 : GC62397
RO0270608，是 R411 的活性代谢物，是一种双重 alpha4beta1-alpha4beta7 (α4β1/α4β7) 整合素拮抗剂。具有抗炎活性。
Cas No.:220846-33-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
RO0270608, the active metabolite of R411, is a dual alpha4beta1-alpha4beta7 (α4β1/α4β7) integrin antagonist. Antiinflammatory activity[1][2].
RO0270608 inhibits α4/β7 mediated cell adhesion with an IC50 of 33 nM. In a human T-cell VCAM/anti CD3 costimulation assay RO0270608 causes a pronounced inhibition of T-cell proliferation (IC50=30 nM)[2].
In a murine OVA-model of airway inflammation, RO0270608 i.n. abolishes allergen-induced inflammatory cell accumulation[2]
[1]. Hijazi Y, et al. Pharmacokinetics, safety, and tolerability of R411, a dual alpha4beta1-alpha4beta7 integrin antagonist after oral administration at single and multiple once-daily ascending doses in healthy volunteers. J Clin Pharmacol. 2004;44(12):1368-1378.
[2]. M. Renzetti, et al. Dual α4/β1-α4/β7 vs α4/β1 selective antagonism is required for attenuation of allergic inflammatory responses. Journal of Allergy and Clinical Immunology. Volume 113, Issue 2, Supplement, February 2004, Page S221.
| Cas No. | 220846-33-3 | SDF | |
| 别名 | (S)-2-(2-氯-6-甲基苯甲酰氨基)-3-(4-(2,6-二氯苯甲酰氨基)苯基)丙酸 | ||
| 分子式 | C24H19Cl3N2O4 | 分子量 | 505.78 |
| 溶解度 | DMSO : 12.5 mg/mL (24.71 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9771 mL | 9.8857 mL | 19.7714 mL |
| 5 mM | 0.3954 mL | 1.9771 mL | 3.9543 mL |
| 10 mM | 0.1977 mL | 0.9886 mL | 1.9771 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacokinetics, safety, and tolerability of R411, a dual alpha4beta1-alpha4beta7 integrin antagonist after oral administration at single and multiple once-daily ascending doses in healthy volunteers
J Clin Pharmacol 2004 Dec;44(12):1368-78.PMID:15545307DOI:10.1177/0091270004270147
R411 is a dual alpha4beta1-alpha4beta7 integrin antagonist under development for the treatment of chronic asthma. The objective of this study was to investigate the pharmacokinetics and safety of R411 and its active metabolite, RO0270608, in humans. A 3-part phase I trial was conducted in 132 healthy volunteers: (1) 12 subjects received 200 mg R411 as a single oral dose or 100 mg RO0270608 as an intravenous infusion in a 1-sequence crossover design; (2) 7 groups of 10 subjects received 1 of 7 single oral doses of R411 (10-1200 mg) in a parallel, placebo-controlled, ascending adaptive dose design; and (3) 5 groups of 10 subjects each received repeated oral qd doses of R411 (50-900 mg) for up to 3 weeks in a parallel, placebo-controlled, ascending adaptive dose design. The absolute bioavailability of RO0270608 (mean +/- standard deviation) after oral administration of R411 was 27% +/- 4%, and the terminal half-life was 7.33 +/- 2.29 hours. After IV infusion of RO0270608, total clearance (mean +/- standard deviation) was 19.4 +/- 7.1 L/h, and the volume of distribution was 93.1 +/- 36.1 L. After single ascending oral doses of R411, area under the concentration-time curve from 0 to infinity of active metabolite RO0270608 increased proportionally from 150 to 1200 mg (P > .05). Following repeated administration, the oral clearance was independent of time. No drug accumulation was observed, and no safety concerns were revealed up to a dose of 900 mg after up to 3 weeks of treatment.