CUDC-101

产品说明书

Print
Chemical Structure| 1012054-59-9 同义名 : -
CAS号 : 1012054-59-9
货号 : A165599
分子式 : C24H26N4O4
纯度 : 99%+
分子量 : 434.488
MDL号 : MFCD15528940
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(57.54 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • HDAC8

    HDAC8, IC50:79.8 nM

  • HDAC10

    HDAC10, IC50:26.1 nM

  • HDAC3

    HDAC3, IC50:9.1 nM

  • HDAC4

    HDAC4, IC50:13.2 nM
描述 CUDC-101 is a potent, multi-acting inhibitor against histone deacetylases (HDAC), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2) with IC50 values of 4.4, 2.4, and 15.7 nM, respectively. CUDC-101 had weak inhibition on the following proteins: KDR (VEGFR2) (849 nM), Src (11000 nM), Lyn (840 nM), Lck (5910 nM), Abl-1 (2890 nM), FGFR-2 (3430 nM), Flt-3 (1500 nM), and Ret (3200 nM). CUDC-101 exhibited strong anti-proliferative activity in many human cancer cell lines with IC50 value ranging from 0.04 – 0.80 μM[3]. The exposure of CUDC-101 (0.1, 1, or 10 μmol/L) for 5 to 24 hours increased acetylation of histone H3 and H4 in various cancer cell lines at a dose-dependent manner. CUDC-101 at 1 μmol/L also inhibited EGFR and HER2 phosphorylation and the level of antiapoptotic proteins, survivin, and Bcl-xL. By treating HCT-116 colon cancer cells with CUDC-101 (0.1, 1, or 10 μmol/L) for 24 hours, the activities of caspases 3 and 7 were significantly increased. In Hep-G2 liver cancer xenograft model, daily administration of 120 mg/kg CUDC-101 for 9 days significantly induced 30% tumor regression. Similarly, CUDC-101 (120 mg/kg/day) treatment showed significant inhibitory effect on tumor growth in A549 NSCLC cell- and MDA-MB-468 breast cancer cell-implanted mice[4].
作用机制 CUDC-101 is a synthesized, multi-targeted inhibitor for HDAC, EGFR, and HER2. The structure of quinazoline is a well-characterized scaffold for the inhibition of EGFR and HER2. By incorporating a hydroxamic acid into the quinazoline pharmacophore with a proper spacer, this compound binds to HDAC to disrupt its enzyme activity[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
human BxPC3 cells Proliferation assay Antiproliferative activity against human BxPC3 cells after hrs by ATP content assay, IC50=0.27 μM 20143778
human Capan1 cells Proliferation assay Antiproliferative activity against human Capan1 cells after hrs by ATP content assay, IC50=0.8 μM 20143778
human H460 cells Proliferation assay Antiproliferative activity against human H460 cells after hrs by ATP content assay, IC50=0.7 μM 20143778
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.30mL

0.46mL

0.23mL

11.51mL

2.30mL

1.15mL

23.02mL

4.60mL

2.30mL
参考文献

[1]Lai CJ, Bao R, et al. CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity. Cancer Res. 2010 May 1;70(9):3647-56.

[2]Cai X, Zhai HX, et al. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J Med Chem. 2010 Mar 11;53(5):2000-9.

[3]Cai X, Zhai HX, Wang J, Forrester J, Qu H, Yin L, Lai CJ, Bao R, Qian C. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J Med Chem. 2010 Mar 11;53(5):2000-9.

[4]Lai CJ, Bao R, Tao X, Wang J, Atoyan R, Qu H, Wang DG, Yin L, Samson M, Forrester J, Zifcak B, Xu GX, DellaRocca S, Zhai HX, Cai X, Munger WE, Keegan M, Pepicelli CV, Qian C. CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity. Cancer Res. 2010 May 1;70(9):3647-56.