| 名称 | CD437 |
| 描述 | CD437 (AHPN) is a specifc Retinoic Acid Receptor γ (RARγ) agonist. |
| 细胞实验 | For morphological analysis, cells are treated with 10 μM CD437, trypsinized, washed with phosphate-buffered saline (PBS), fixed with 3.7% paraformaldehyde, and stained with 50 μg of 4,6-diamidino-2-phenylindole (DAPI) per mL containing 100 μg of DNase-free RNase A per mL to visualize the nuclei. Stained cells are examined by fluorescence microscopy. For the terminal deoxynucleotidyl transferase (TdT) assay, cells are treated with or without 10 μM CD437. After treatment, cells are trypsinized, washed with PBS, fixed in 1% formaldehyde in PBS, washed with PBS, resuspended in 70% ice-cold ethanol, and immediately stored at -20°C overnight. Cells are then labeled with biotin-16-dUTP by terminal transferase and stained with avidin-FITC (fluorescein isothiocyanate). |
| 激酶实验 | Forty microliter enzyme buffer (15 mM Tris HCl pH 8.1, 0.25 mM EDTA, 250 mM NaCl, 10% v:v glycerol) containing HDAC1, 3, 6 or 8 activity, 29 μL enzyme buffer and 1 μL resminostat [HCl] at different concentrations are added to a 96-well microtitre plate and the reaction started by the addition of 30 μL substrate peptide Ac-NH-GGK(Ac)-AMC (HDAC1, 3 and 6 assays, final concentrations 6 μM for HDAC1, 10 μM for HDAC6 and 25 μM for HDAC3/DAD) or Ac-RHK(Ac)K(Ac)-AMC (HDAC8 assay, final concentration 50 μM). After incubation for 180 min (HDAC1, HDAC6, HDAC8) or 120 min (HDAC3) at 30°C, the reaction is terminated by the addition of 25 μL stop solution (50 mM Tris HCl pH 8, 100 mM NaCl, 0.5 mg/mL trypsin and 2 μM trichostatin A [TSA]). After incubation at room temperature for further 40 min, fluorescence is measured using a Wallac Victor2 1420 multilabel counter (extinction 355 nm, emission 460 nm) for quantification of AMC generated by tryptic cleavage of the deacetylated peptide. For the calculation of the 50% inhibitory concentration (IC50) values the fluorescence in wells without test compound (1% DMSO, negative control) is set as 100% enzymatic activity and the fluorescence in wells with 2 μM TSA (positive control) are set at 0% enzymatic activity (background fluorescence substracted). |
| 动物实验 | Male Swiss-nu/nu mice weighing 20 to 25 g are used in this study. Mice are kept under sterile conditions at 24 to 26°C room temperature, 50% relative humidity, and 12 h light-dark rhythm in laminar flow shelves and are supplied with autoclaved food and bedding. For treatment of melanoma xenografts, previously established MeWo melanoma tumors of 1 to 2 mm in diameter are implanted into the right flank of animals. After tumor growth for 10 d, groups of mice (n=8) are either treated with saline p.o. or are injected intratumorally for 3 wk or are fed with various concentrations of CD437 (10 mg/kg/body weight and 30 mg/kg/body weight). In addition, tumors of a fifth group are injected with CD437 (10 mg/kg/body weight) each day. Mice are visited daily and growing tumors are measured twice weekly with a caliperlike instrument. |
| 体外活性 | CD437 (10 µM，2天) 抑制这些肺癌细胞系的生长。剂量-反应实验显示，CD437减少了H460/SK-MES-1/A549/H292细胞数量（IC50：0.5/0.4/3/0.85 µM）。用CD437处理72小时，对所有黑色素瘤细胞系均表现出强烈的剂量依赖性生长抑制。在5 µM CD437浓度下，仅约5至25%的细胞在3天后保持存活。CD437所需的IC50浓度范围从对MeWo的10 µM到对SK-Mel-23的0.1 µM，显示出最高的敏感性。 |
| 体内活性 | 在CD437处理的小鼠中，肿瘤停止生长，该效果在首次给药后的第3天和第13天已达到统计学意义（P<0.01），并在停药后3周以上仍然维持。组织学分析显示，CD437处理的肿瘤中，肿瘤-基质边缘处的c-fos mRNA水平显著增高。 |
| 存储条件 | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 127.5 mg/mL (319.96 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.02 mM), Sonication is recommended.
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| 关键字 | RetinoidReceptor | Retinoid X receptors | Retinoid Receptor | Retinoic acid receptors | RARγ | RAR/RXR | Inhibitor | inhibit | CD-437 | CD437 | CD 437 | Autophagy |
| 相关产品 | Oxyresveratrol | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
| 相关库 | 脂代谢化合物库 | 经典已知活性库 | 抗癌活性化合物库 | 已知活性化合物库 | 转录因子库 | 自噬库 | 代谢化合物库 | 临床前化合物库 | NO PAINS 化合物库 | 抗代谢疾病化合物库 | 表型筛选靶点鉴定库 | 细胞重编程化合物库 |