AM095
(Synonyms: 4'-[3-甲基-4-[[[(1R)-1-苯基乙氧基]羰基]氨基]-5-异恶唑基]联苯-4-乙酸钠盐,AM 095;AM-095) 目录号 : GC15220
AM095是一种选择性、具有口服活性的LPA1受体拮抗剂，对小鼠LPA1的IC50值为0.73μM。
Cas No.:1345614-59-6
Sample solution is provided at 25 µL, 10mM.
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AM095 is a selective, orally bioavailable LPA1 antagonist with an IC50 value of 0.73μM for mouse LPA1[1]. AM095 can reduce the mRNA expression level of pro-inflammatory cytokines and inhibit the activation of NF-κB by antagonizing LPA1 activity[2]. AM095 has been widely used to inhibit the development of idiopathic pulmonary fibrosis and systemic fibrosis in different animal models[3].
In vitro, AM095 treatment (10μM) for 48h significantly inhibited Lysophosphatidic acid (LPA)-induced decrease in E-cadherin expression and reduced the expression levels of fibrosis factors (α-SMA and fibronectin)[4]. Pretreatment with 0.5µM AM095 for 3 hours significantly reversed Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced decline in the viability of periodontal ligament stem cells (PDLSCs) and reduced the expression of IL-1β and TNF-α[5]. Pretreatment of MDA-MB-231 cells with 0.5µM AM095 for 5min significantly inhibited the proliferation of MDA-MB-231 cells induced by 30µM lysophosphatidylethanolamine (LPE) (24h)[6].
In vivo, AM095 treatment via oral administration at a dose of 30mg/kg/day for 8 weeks alleviated hyperglycemia and dyslipidemia and improved renal function in streptozotocin (STZ)-induced diabetic mice[7]. Gavage of AM095 at a dose of 10mg/kg once daily for 18 days reduced disease severity and increased the number of redifferentiated Schwann cells in a rat model of induced experimental autoimmune neuritis[8].
References:
[1] Swaney J S, Chapman C, Correa L D, et al. Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist[J]. The Journal of pharmacology and experimental therapeutics, 2011, 336(3): 693-700.
[2] Gaire B P, Sapkota A, Song M R, et al. Lysophosphatidic acid receptor 1 (LPA1) plays critical roles in microglial activation and brain damage after transient focal cerebral ischemia[J]. Journal of Neuroinflammation, 2019, 16(1): 170.
[3] Im D S. First-in-class antifibrotic therapy targeting type 1 lysophosphatidic acid receptor[J]. Archives of pharmacal research, 2012, 35(6): 945-948.
[4] Lee G H, Cheon J, Kim D, et al. Lysophosphatidic Acid Promotes Epithelial–Mesenchymal Transition in Kidney Epithelial Cells via the LPAR1/MAPK-AKT/KLF5 Signaling Pathway in Diabetic Nephropathy[J]. International Journal of Molecular Sciences, 2022, 23(18): 10497.
[5] Kim D H, Seo E J, Tigyi G J, et al. The role of lysophosphatidic acid receptor 1 in inflammatory response induced by lipopolysaccharide from Porphyromonas gingivalis in human periodontal ligament stem cells[J]. Intern J Oral Biol, 2020, 45: 42-50.
[6] Park S J, Lee K P, Im D S. Action and signaling of lysophosphatidylethanolamine in MDA-MB-231 breast cancer cells[J]. Biomolecules & Therapeutics, 2014, 22(2): 129.
[7] Lee J H, Sarker M K, Choi H, et al. Lysophosphatidic acid receptor 1 inhibitor, AM095, attenuates diabetic nephropathy in mice by downregulation of TLR4/NF-κB signaling and NADPH oxidase[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2019, 1865(6): 1332-1340.
[8] Szepanowski F, Winkelhausen M, Steubing R D, et al. LPA1 signaling drives Schwann cell dedifferentiation in experimental autoimmune neuritis[J]. Journal of Neuroinflammation, 2021, 18(1): 293.
AM095是一种选择性、具有口服活性的LPA1受体拮抗剂，对小鼠LPA1的IC50值为0.73μM[1]。AM095通过拮抗LPA1活性，可降低促炎细胞因子的mRNA表达水平并抑制NF-κB活化[2]。AM095已广泛应用于多种动物模型中抑制特发性肺纤维化和系统性纤维化的进展[3]。
在体外，使用10μM的AM095处理48小时能显著抑制Lysophosphatidic acid (LPA)诱导的E-钙黏蛋白表达下降，并降低纤维化因子（α-SMA和纤连蛋白）的表达水平[4]。用0.5μM的AM095预处理人牙周膜干细胞(PDLSCs)3小时，可显著逆转牙龈卟啉单胞菌脂多糖(Pg-LPS)诱导的细胞活力下降，并减少IL-1β和TNF-α的表达[5]。以0.5μM的AM095预处理MDA-MB-231细胞5分钟，能显著抑制30µM的lysophosphatidylethanolamine (LPE)处理24小时诱导的细胞增殖[6]。
在体内，每日口服30mg/kg/day剂量的AM095连续8周，可缓解链脲佐菌素(STZ)诱导的糖尿病小鼠的高血糖和血脂异常，并改善肾功能[7]。在实验性自身免疫性神经炎大鼠模型中，每日灌胃10mg/kg 剂量的AM095连续18天，能减轻疾病严重程度并增加去分化雪旺细胞的数目[8]。
| Cell experiment [1]: | |
Cell lines | HK-2 cells |
Preparation Method | HK-2 cells were cultured in RPMI-1640 medium containing 5% fetal bovine serum and 1% penicillin-streptomycin in a humidified environment at 37℃, 5% CO2, and 95% air. HK-2 cells (1×105 cells in a 60-mm dish) were seeded and cultured for 24 hours. The medium was then replaced with serum-free medium (SFM) containing 0.1% fatty acid-free bovine serum albumin (BSA), and the culture was continued for 17 to 18 hours. HK-2 cells were treated with 20µM LPA in the presence or absence of 10µM AM095 for 48 hours and then analyzed for changes in the expression levels of EMT markers and fibrosis factors. |
Reaction Conditions | 10µM; 48h |
Applications | AM095 treatment significantly inhibited LPA-induced decrease in E-cadherin expression and reduced the expression levels of fibrosis factors (α-SMA and fibronectin). |
| Animal experiment [2]: | |
Animal models | Male C57BL/6J mice |
Preparation Method | Eight-week-old male C57BL/6J mice were intraperitoneally injected with STZ at a dose of 50mg/kg for 5 consecutive days after a 4-h early morning fast. Diabetes was diagnosed when blood glucose levels were>350mg/dl. Subsequently, STZ-diabetic mice with similar body weight were randomly divided into three groups: STZ-vehicle group, STZ-AM095 treatment group, and STZ-losartan treatment group. Age-matched non-diabetic C57BL/6J male mice were used as the vector control group. AM095 was orally administered daily in the early morning at a dose of 30 mg/kg/day, losartan 10 mg/kg treatment group, for 8 weeks. Blood glucose, blood lipid, and renal function of mice were analyzed. |
Dosage form | 30mg/kg/day for 8 weeks; p.o. |
Applications | AM095 treatment alleviated hyperglycemia and dyslipidemia and improved renal function in STZ-induced diabetic mice. |
References: | |
| Cas No. | 1345614-59-6 | SDF | |
| 别名 | 4'-[3-甲基-4-[[[(1R)-1-苯基乙氧基]羰基]氨基]-5-异恶唑基]联苯-4-乙酸钠盐,AM 095;AM-095 | ||
| 化学名 | sodium;2-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate | ||
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2)C3=CC=C(C=C3)C4=CC=C(C=C4)CC(=O)[O-].[Na+] | ||
| 分子式 | C27H23N2NaO5 | 分子量 | 478.47 |
| 溶解度 | ≥ 23.9 mg/mL in DMSO, ≥ 16.77 mg/mL in EtOH with ultrasonic | 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 | 2.09 mL | 10.45 mL | 20.9 mL |
| 5 mM | 418 μL | 2.09 mL | 4.18 mL |
| 10 mM | 209 μL | 1.045 mL | 2.09 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。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
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