<noframes id="7dr1n">

<noframes id="7dr1n">
<form id="7dr1n"></form>
      ?

      产品搜索:

      手机:18001401806;18915562593

      电话: 0517-86993111;0512-62729923

      传真: 0512-62729923

      联系人: 贾经理;胡总

      邮编: 215000

      地址: 江苏省苏州市工业园区仁爱路150号C316室

      当前位置>>返回首页

      Chinese Name

      中文名


      恩替诺特

      English Name

      英文名


      Pyridin-3-ylmethyl 4-(2-aminophenylcarbamoyl)benzylcarbamate

      Alias

      别名


      [[4-[[(2-aminophenyl)amino]carbonyl]phenyl]methyl]- Carbamic acid 3-pyridinylmethyl ester; Entinostat; MS27-275; MS 275; MS 275-27; SNDX 275


      CAS NO.


      209783-80-2

      Formula

      分子式


      C21H20N4O3

      M.W.

      分子量


      376.41

      Class

      分类


      原料药



      MS-275 is an inhibitor of HDAC (histone deacetylase) that preferentially inhibits HDAC1 (IC50 = 300 nM) over HDAC3 (IC50 = 8 μM). However, MS-275 does not inhibit HDAC8 (IC50 > 100 μM). MS-275 induces cyclin-dependent kinase inhibitor 1A (p21/CIP1/WAF1), slowing cell growth, differentiation, and tumor development in vivo. Recent studies suggest that MS-275 may be particularly useful as an antineoplastic agent when combined with other drugs, like adriamycin, inhibitors of poly (ADP-ribose) polymerase (PARP), or inhibitors of heat shock protein 90 (Hsp90).
      产品描述 MS-275抑制HDACs,作用于HDAC1和HDAC3时,IC50分别为0.51 μM和1.7 μM。
      靶点 HDAC1 HDAC3 
      IC50 0.51 μM 1.7 μM [2] 
      体外研究 MS-275通过作用于2′-氨基而抑制HDACs。MS-275作用于 K562细胞,诱导 p21WAF1/CIP1和凝溶胶蛋白的累积。MS-275作用于A2780细胞,可以降低S期细胞,提高G1期细胞。 MS-275通过抑制HAD而抑制人类肿瘤细胞系,包括 A2780, Calu-3, HL-60, K562, St-4, HT-29, KB-3-1, Capan-1, 4-1St和 HCT-15细胞增殖, IC50 为41.5 nM到4.71 μM。[1]MS-275抑制HDACs,作用于HDAC1和 HDAC3时IC50 分别为0.51 μM和1.7 μM。而对其他的HDACs没有抑制效果,如HDAC4, 6, 8和10。[2]MS-275有效抑制人类白血病和淋巴癌细胞,包括U937, HL-60, K562, 和Jurkat。MS-275可以诱导U937细胞p21CIP1/WAF1 调节的生长和变异Marker (CD11b)的表达。MS-275降低cyclin D1和抗凋亡蛋白Mcl-1与XIAP的表达。[3]
      体内研究 MS-275按49 mg/kg剂量作用于除了HCT-15的人类移植瘤都显示出强抗癌活性。[1]MS-275促进恶性实体瘤和恶性血液病的治疗可能性,及生理和畸变基因表达的调节。MS-275和IL-2联用,作用于肾细胞癌显示出强抗癌活性,因为降低调节性T细胞和增强脾细胞的表达。临床实验 MS-275和5-氮杂胞苷联用用于治疗周期性非小细胞肺癌目前处于I/II期临床实验阶段。
      特征 
      推荐的实验操作
      激酶实验:  
      标准HDAC实验 用HDAC buffer按1:6稀释鼠肝内的酶。重组人类HDACs按1:4稀释在HDAC buffer中。用于标准HDAC实验,60 μl HDAC buffer和10 μl 稀释的酶溶液在30oC混合。在HDAC buffer中加入30 μl基底液开始HDAC反应,随后在30oC下温育30分钟。加入100 μl胰蛋白酶溶液终止反应,胰蛋白酶溶液由溶于50 mM Tris-HCl(pH 为8.0)的10 mg/ml 胰蛋白酶, 100 mM NaCl,及 2 μM TSA组成。30oC下温育20分钟, 通过测定460纳米(λex = 390 nm)处的荧光监测AMC的释放。使用释放的AMC校准荧光强度 。用于标准时间过程实验,在初始100 μl HDAC 反应中加入20 pmol 基底物。2-50 pmol 基底物的酶法分析产物获得荧光AMC,通过测量这种荧光AMC来测定 Km值和 Vmax值。使用Hanes 图分析实验数据。记录的AMC信号是针对没有酶而有buffer和基底物的空白区。
      细胞试验: [2]
      细胞系 A2780, Calu-3, HL-60, K562, St-4, HT-29, KB-3-1, Capan-1, 4-1St和HCT-15细胞
      浓度 10 μM 左右
      处理时间 3天
      方法 5×103个肿瘤细胞接种到96孔板上,加入梯度浓度MS-275培养三天。细胞用0.1 mg/mL中性红在CO2反应器中染色1小时,测定中性红与50 μL乙醇和150 μL 0.1 M Na2HPO4溶解后的OD540,测定IC50值。
      动物实验:  
      动物模型 侧腹皮下注射A2780, HT-29, HTC-15, KB-3-1, 4-1St, St-4, Capan-1和Calu-3细胞的裸鼠
      配制 溶于0.05 N HCl, 0.1% Tween-80
      剂量 12.3, 24.5和49 mg/kg
      给药处理 每天口服处理一次,每周进行5天,持续4周。
      溶解性 (25°C)
      ? DMSO 75 mg/mL
      ? 水 <1 mg/mL
      ? 乙醇 <1 mg/mL
      稳定性 2年 -20°C粉状
      2周4°C溶于DMSO
      6月-80°C溶于DMSO

      1.Biochemical and Biophysical Research Communications, 414 (2011) 25–30. 
      2.Breast Cancer Res Treat , 2010, 131(3), 777-789. 
      3.Sci Signal, 2010, 3, ra80. 
      4.Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. [Bantscheff M, et al. Nat Biotechnol 2011;29(3), 255-265] PubMed: 21258344
      5.Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors. [Lee JH, et al. Proc Natl Acad Sci U S A 2011;108(49):19629-34] PubMed: 22106282
      6.Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism. [Cavasin MA, et al. Circ Res 2012;110(5):739-48] PubMed: 22282194
      7.Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition. [Engmann O, et al. Brain 2011;134(Pt 8):2408-21] PubMed: 21772061
      8.Histone deacetylase inhibitors preserve white matter structure and function during ischemia by conserving ATP and reducing excitotoxicity. [Baltan S, et al. J Neurosci 2011;31(11):3990-9] PubMed: 21411642
      9.DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination. [Du Z, et al. Sci Signal 2010;3(146), ra80] PubMed: 21045206
      10.IL-10 Regulates Il12b Expression via Histone Deacetylation: Implications for Intestinal Macrophage Homeostasis. [Kobayashi T, et al. J Immunol 2012;189(4):1792-9] PubMed: 22786766
      11.RSK2Ser227 at N-terminal kinase domain is a potential therapeutic target for multiple myeloma. [Shimura Y, et al. Mol Cancer Ther 2012;11(12):2600-9] PubMed: 23012246
      12.Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. [Huang Y, et al. Breast Cancer Res Treat 2012;131(3), 777-789] PubMed: 21452019
      13.Histone Deacetylase Inhibitors (HDACis) That Release the Positive Transcription Elongation Factor b (P-TEFb) from Its Inhibitory Complex Also Activate HIV Transcription. [Bartholomeeusen K, et al. J Biol Chem 2013;288(20), 14400-14407] PubMed: 23539624
      14.Histone Deacetylase Inhibitors (HDACis) That Release the Positive Transcription Elongation Factor b (P-TEFb) from Its Inhibitory Complex Also Activate HIV Transcription. [Bartholomeeusen K, et al. J Biol Chem 2013;288(20), 14400-7] PubMed: 23539624
      15.Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. [Brazelle W, et al. PLoS One 2010;5(12), e14335] PubMed: 21179472
      16.Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors. [MacTavish H, et al. PLoS One 2010;5(12), e14462] PubMed: 21283510
      17.Inhibition of class II histone deacetylases in the spinal cord attenuates inflammatory hyperalgesia. [Bai G, et al. Mol Pain 2010;6, 51] PubMed: 20822541
      18.Histone deacetylase inhibitors preserve function in aging axons. [Baltan S, et al. J Neurochem 2012;123 Suppl 2:108-15] PubMed: 23050648
      19.Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib. [Suda K, et al. J Thorac Oncol 2011;6(7):1152-61] PubMed: 21597390
      20.Sca-1 is an early-response target of histone deacetylase inhibitors and marks hematopoietic cells with enhanced function. [Walasek MA, et al. Exp Hematol 2013;41(1):113-23.e2] PubMed: 22989761
      21.Differential regulation of theSMN2 gene by individual HDAC proteins. [Evans MC, et al. Biochem Biophys Res Commun 2011;414(1):25-30]  PubMed: 21925145
      22.Histone Deacetylase Activity Selectively Regulates Notch-Mediated Smooth Muscle Differentiation in Human Vascular Cells. [Tang Y, et al. J Am Heart Assoc 2012;1(3):e000901] PubMed: 23130137






















      ?

      地址: 江苏省苏州市工业园区仁爱路150号C316室 电话:0517-86993111;0512-62729923

      版权所有:苏州东南药业股份有限公司 备案号:<a href="http://beian.miit.gov.cn" target="_blank">苏ICP备19046012号-1</a> 技术支持:苏州开创网络

      水果机 <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <蜘蛛词>| <文本链> <文本链> <文本链> <文本链> <文本链> <文本链>