AM580
(Synonyms: 4-[(5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基)甲酰氨基]苯甲酸,CD336; NSC608001; Ro 40-6055) 目录号 : GC13664
A selective RARα agonist
Cas No.:102121-60-8
Sample solution is provided at 25 µL, 10mM.
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AM580 is a selective agonist of retinoic acid receptor α (RARα) with IC50 and EC50 values of 8 nM and 0.36 nM, respectively [1].
RARα is ubiquitously expressed. It is important for retinoid response during growth and differentiation of epithelial cells. RARα have functions in the inhibition of cell and mammary tumour growth, increase in tumour latency, induction of cell cycle arrest, stimulation of cell death, and up-regulation of RARα and RARγ mRNA [1, 2]. In addition, RARα is involved in the production of human T cell activation and type 2 cytokine [3].
In SK-BR-3 and T47D breast cancer cell lines, treatment with AM580 at concentrations of 1 nM and 10 nM for 7 days resulted in the decrease in the number of cells [1]. AM580 at a concentration of 200 nM, enhanced the anti-proliferative effect shown by the knockdown of RAR-γ in MCF-10A breast epithelial and MCF-7 cell lines [2].
When 200 nM AM580 was applied to MMTV-Myc female mice for 96 hours, this led to impaired cell proliferation capacity. Furthermore, combination of AM580 with 100 nM CD437 and SR11253 resulted in strong growth inhibition, clearly demonstrating the ability of AM580 to reduce the tumour growth in MMTV-Myc tumour model [2].
References:
[1]. Schneider S, Offterdinger M, Huber H, et al. Activation of Retinoic Acid Receptor a Is Sufficient for Full Induction of Retinoid Responses in SK-BR-3 and T47D Human Breast Cancer Cells. Cancer Res, 2000, 60(19):5479-87.
[2]. Bosch A, Bertran S, Lu Y, et al. Reversal by RARa agonist Am580 of c-Myc induced imbalance in RARa/RARγ expression during MMTV-Myctumorigenesis. Breast Cancer Res, 2012, 14(4):R121.
[3]. Dawson H, Collins G, Pyle R, et al. The Retinoic Acid Receptor-α mediates human T-cell activation and Th2 cytokine and chemokine production. BMC Immunol, 2008, 9:16.
Kinase experiment: | Approximately 1×106 NB4, HL-60, and APL fresh leukemic cells or CML neutrophils are harvested, pelletted by centrifugation at 400 g for 10 minutes, washed once with 0.9% NaCl, and centrifuged again. The washed cell pellet is resuspended in homogenization buffer (1 mM MgCl2, 1 mM CaCl2, 20 mM ZnCl2, 0.1 mM NaCl, 0.1% [vol/vol] Triton X-100, 50 mM Tris/HCl, pH 7.4) and disrupted by vigorous pipetting. The homogenate is used for the LAP assay, which is performed with p-nitrophenol phosphate as substrate according to the instructions of the manufacturer. LAP activity is normalized for the content of protein in the sample. Proteins are measured according to the Bradford method using BSA fraction V as a standard. One unit of LAP activity is defined as the amount of enzyme capable of transforming 1 nmol of substrate in 1 minute at 25°C. Enzyme assays are performed in conditions of linearity relative to the substrate and to the concentration of proteins. |
Cell experiment: | MCF-10A (2×104) control cells or overexpressing RARγ are seeded in triplicates in 6-well culture dishes. After 24 hrs, cells are washed with PBS, incubated in 2 mL of DMEM-F12 culture medium, detached and counted every 24 hrs. Statistical significance is determined by t-test. pRB and p27 expression is tested by immunofluorescence analysis of control MCF-10A monolayers and monolayers stably transfected with pSG5-RARγ expression vector, using the same antibodies described for the IHC analysis. |
Animal experiment: | Four months old uniparous (1 pregnancy/lactation cycle) MMTV-neu and 6 weeks old nulliparous MMTV-wnt1 female mice (50 mice/group) are treated with the RARα agonist AM580 (0.3 mg/kg body weight per mouse per day) in the diet (Purina 5053) by adding 1.5 mg AM580 per kg of Purina 5053 diet. Mice that develop tumors within the first month of treatment are removed from the study. Mice are palpated twice a week and tumor appearance is recorded. Once palpable, the size of the tumors is measured weekly. Tumor-free survival is calculated from Kaplan-Meier curves and statistical significance is determined by the Log-rank test for the survival studies and t-test for the tumor growth studies. Metastasis is evaluated by removing the lungs of all the anesthetized mice, selecting randomLy 20 mice per group and inspecting the lung surface for lesions using a stereoscope. |
References: [1]. Gianní M, et al. AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. Blood. 1996 Feb 15;87(4):1520-31. | |
| Cas No. | 102121-60-8 | SDF | |
| 别名 | 4-[(5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基)甲酰氨基]苯甲酸,CD336; NSC608001; Ro 40-6055 | ||
| Canonical SMILES | O=C(C1=CC=C2C(C)(C)CCC(C)(C)C2=C1)NC3=CC=C(C(O)=O)C=C3 | ||
| 分子式 | C22H25NO3 | 分子量 | 351.44 |
| 溶解度 | ≥ 14.3mg/mL in DMSO | 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 | 2.8454 mL | 14.2272 mL | 28.4544 mL |
| 5 mM | 0.5691 mL | 2.8454 mL | 5.6909 mL |
| 10 mM | 0.2845 mL | 1.4227 mL | 2.8454 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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet