| 名稱 | CD437 |
| 描述 | CD437 (AHPN) is a specifc Retinoic Acid Receptor γ (RARγ) agonist. |
| 細(xì)胞實(shí)驗(yàn) | 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). |
| 激酶實(shí)驗(yàn) | 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). |
| 動(dòng)物實(shí)驗(yàn) | 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. |
| 體外活性 | CD437 (10 μM，2天) 抑制這些肺癌細(xì)胞系的生長。劑量-反應(yīng)實(shí)驗(yàn)顯示，CD437減少了H460/SK-MES-1/A549/H292細(xì)胞數(shù)量（IC50：0.5/0.4/3/0.85 μM）。用CD437處理72小時(shí)，對所有黑色素瘤細(xì)胞系均表現(xiàn)出強(qiáng)烈的劑量依賴性生長抑制。在5 μM CD437濃度下，僅約5至25%的細(xì)胞在3天后保持存活。CD437所需的IC50濃度范圍從對MeWo的10 μM到對SK-Mel-23的0.1 μM，顯示出最高的敏感性。 |
| 體內(nèi)活性 | 在CD437處理的小鼠中，腫瘤停止生長，該效果在首次給藥后的第3天和第13天已達(dá)到統(tǒng)計(jì)學(xué)意義（P<0.01），并在停藥后3周以上仍然維持。組織學(xué)分析顯示，CD437處理的腫瘤中，腫瘤-基質(zhì)邊緣處的c-fos mRNA水平顯著增高。 |
| 存儲(chǔ)條件 | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 60 mg/mL (150.57 mM)
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| 關(guān)鍵字 | inhibit | Retinoid X receptors | CD437 | RAR/RXR | Inhibitor | Autophagy | Retinoic acid receptors | CD-437 | CD 437 |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Salicylic acid | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 脂代謝化合物庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 抗癌化合物庫 | 已知活性化合物庫 | 自噬庫 | 代謝化合物庫 | 抗代謝疾病化合物庫 | 神經(jīng)元分化化合物庫 | 細(xì)胞重編程化合物庫 |