AM966
(Synonyms: 4'-[4-[[[(1R)-1-(2-氯苯基)乙氧基]羰基]氨基]-3-甲基-5-异恶唑基]-联苯-4-乙酸,AM 966;AM-966) 目录号 : GC13476
A potent and selective LPA1 receptor antagonist
Cas No.:1228690-19-4
Sample solution is provided at 25 µL, 10mM.
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AM966 is a selective, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (LPA1) with IC50 values of 17 and 19 nM for human or mouse LPA1, respectively [1]. Relative to LPA2, 3, 4, 5 receptors, AM966 shows 10-fold and 100-fold more selective in mouse and human cell lines for LPA1, respectively [1].
In vitro, AM966 shows to inhibit LPA-induced chemotaxis in IMR-90 human lung fibroblasts, A2058 human melanoma cells and CHO cells expressing LPA1 receptors [1].
In vivo, AM966 has been demonstrated to reduce total BALF cells, LDH activity, BALF collagen and total TGFβ concentrations in bleomycin-induced mice. Moreover, AM966 has been reported to block lung fibrosis, reduce lung inflammation and maintain body weight in mice induced by bleomycin [1].
Reference:
[1] Swaney JS1, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH, Seiders TJ,Parr TA, Prasit P, Evans JF, Lorrain DS. A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010 Aug;160(7):1699-713.
| Cell experiment: [1] | |
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Cell lines |
CHO cells (stably expressing human LPA1 or mouse LPA1) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
100 nM, 30 min for 100% calcium release inhibition 469 nM, 15 min for chemotaxis inhibition (IC50) |
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Applications |
CHO cells were pre-treated with increasing concentrations of AM966 for 30 min and then stimulated with LPA (10–30 nM) and calcium release was measured. AM966 inhibited LPA-stimulated intracellular calcium release from CHO cells stably expressing human and mouse LPA1 receptors. AM966 was also evaluated for inhibition of LPA-induced chemotaxis in CHO cells stably expressing mouse LPA1 receptors. The IC50 value was 469±54 nM. |
| Animal experiment: [1] | |
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Animal models |
Female C57BL/6 mice |
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Dosage form |
Oral administration, 30 or 60 mg/kg, twice daily |
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Applications |
No reduction in lung fibrosis was observed in response to low dose AM966 (10 mg·kg-1). However, AM966 at 30 and 60 mg·kg-1 dramatically reduced lung tissue remodelling and fibrosis so that lung architecture in these groups was similar to that of the vehicle group. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Swaney J S, Chapman C, Correa L D, et al. A novel, orally active LPA1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. British journal of pharmacology, 2010, 160(7): 1699-1713. | |
| Cas No. | 1228690-19-4 | SDF | |
| 别名 | 4'-[4-[[[(1R)-1-(2-氯苯基)乙氧基]羰基]氨基]-3-甲基-5-异恶唑基]-联苯-4-乙酸,AM 966;AM-966 | ||
| 化学名 | 2-[4-[4-[4-[[(1R)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid | ||
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)O | ||
| 分子式 | C27H23ClN2O5 | 分子量 | 490.93 |
| 溶解度 | ≥ 24.55 mg/mL in DMSO, ≥ 2.24 mg/mL in EtOH with ultrasonic and warming | 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 | 2.037 mL | 10.1848 mL | 20.3695 mL |
| 5 mM | 0.4074 mL | 2.037 mL | 4.0739 mL |
| 10 mM | 0.2037 mL | 1.0185 mL | 2.037 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet