dBET1

• 常用名: dBET1
• 英文名: dBET1
• CAS号: 1799711-21-9
• 分子量: 785.268
• 密度: 1.6±0.1 g/cm3
• 沸点: N/A
• 分子式: C₃₈H₃₇ClN₈O₇S
• 熔点: N/A
• 闪点: N/A

dBET1用途

dBET1 是基于 PROTAC 技术的有效的 BRD4 蛋白质降解物,其 EC50 值为 430 nM。

dBET1名称

• 中文名: dBET1
• 英文名: dBET1

dBET1生物活性

• 描述: dBET1 是基于 PROTAC 技术的有效的 BRD4 蛋白质降解物,其 EC50 值为 430 nM。
• 相关类别:
  信号通路 >> 表观遗传学 >> 表观遗传读者域
  信号通路 >> 蛋白裂解靶向嵌合体 >> PROTAC
  研究领域 >> 癌症
• 靶点实验:

  EC50: 430 nM (BRD4)[1]

• 体外研究: 用dBET1治疗下调MYC和PIM1转录。通过dBET1降解BRD4与MV4; 11细胞系中更有效的细胞凋亡结果相关。仅在4小时的dBET1处理后,在8小时时,细胞凋亡显着增加。 dBET1还诱导对MV4的有效和优异的抑制作用; 24小时时11细胞增殖(通过ATP含量测量,IC 50 =0.14μM,与IC 50 =1.1μM与JQ1相比)[1]。
• 体内研究: 如通过连续体积测量所确定的,给予dBET1减弱肿瘤进展,并且降低死后评估的肿瘤重量。在用dBET1(50mg/kg IP)进行第一次或第二次每日治疗后4小时观察到BRD4的急性药效学降解。与切除的肿瘤中的载体对照相比,用dBET1观察到BRD4的统计学显着的去稳定化,MYC的下调和增殖的抑制。小鼠对两周的dBET1耐受良好,对体重,白细胞计数,血细胞比容或血小板计数没有显着影响[1]。
• 参考文献:

  [1]. Winter GE, et al. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015 Jun 19;348(6241):1376-81.

dBET1物理化学性质

• 密度: 1.6±0.1 g/cm3
• 分子式: C₃₈H₃₇ClN₈O₇S
• 分子量: 785.268
• 精确质量: 784.219421
• LogP: 1.98
• InChIKey: LKEGXJXRNBALBV-PMCHYTPCSA-N
• SMILES: Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=NC(CC(=O)NCCCCNC(=O)COc1cccc3c1C(=O)N(C1CCC(=O)NC1=O)C3=O)c1nnc(C)n1-2
• 折射率: 1.746
• 储存条件: 2-8℃

dBET1靶点实验

查看更多实验

实验名称：Stability of compound in DMSO at 10 uM incubated for 12 hrs by LC-MS analysis 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672009

实验名称：Drug metabolism of the compound in PBS/ACN assessed as compound degradation by measur... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672008

实验名称：Protac activity at CRBN/BRD4 in human MV4-11 cells assessed as induction of BRD4 prot... 来源：ChEMBL 靶标：Protein cereblon External Id：CHEMBL5240578

实验名称：Metabolic stability in cryopreserved human hepatocytes assessed as half-life at 1 uM ... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672001

实验名称：Protac activity at CRBN/BRD4 in human MV4-11 cells assessed as induction of BRD4 prot... 来源：ChEMBL 靶标：Protein cereblon External Id：CHEMBL5240577

实验名称：Stability of the compound in PBS/ACN assessed as compound degradation at 10 uM measur... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672005

实验名称：Stability of the compound in PBS at pH 7.4 assessed as compound degradation at 10 uM ... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672004

实验名称：Drug metabolism of compound in PBS/ACN-DMSO assessed as hydrolysis of phthalimide gro... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672007

实验名称：Stability of compound in PBS/ACN-DMSO assessed as compound degradation at 10 uM measu... 来源：ChEMBL 靶标：N/A External Id：CHEMBL4672006

实验名称：Protac activity at CRBN/BRD4 in human MM1.S cells assessed as induction of BRD4 prote... 来源：ChEMBL 靶标：Protein cereblon External Id：CHEMBL5240570

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dBET1英文别名

• 2-[(6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-{4-[({[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]oxy}acetyl)amino]butyl}acetamide