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Chemical Structure| 1339928-25-4 同义名 : CUDC-907
CAS号 : 1339928-25-4
货号 : A175209
分子式 : C23H24N8O4S
纯度 : 99%+
分子量 : 508.553
MDL号 : MFCD22420823
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(98.32 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

DMF: 5 mg/mL(9.83 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • p110β

    PI3Kβ, IC50:54 nM

  • p110α

    PI3Kα, IC50:19 nM

  • p110δ

    PI3Kδ, IC50:39 nM

  • HDAC10

    HDAC10, IC50:2.8 nM
描述 PI3K pathway plays an important role in cancer cell initiation, growth, proliferation, and survival. HDACs can affect a variety of cell functions, by regulating both histone and nonhistone substrates, and synergize with PI3K. CUDC-907 is a dual inhibitor of both class I/ II HDACs, IC50 of 1.7 nM，5 nM，1.8 nM， 27 nM，2.8 nM and 5.4 nM for HDAC1，HDAC2，HDAC3，HDAC7，HDAC10 and HDAC11 and class I PI3Ks, IC50 of 19 nM, 54 nM, and 39 nM for PI3Ka, PI3Kb, and PI3Kd, respectively. Similar to other pan-HDAC inhibitors, CUDC-907 markedly increased acetylated histones as well as non-histone proteins such as tubulin and p53 and also induced p21 protein expression in H460 cell lines at concentration of 1 μM. As a PI3K inhibitor, CUDC-907 decreased phosphorylation of AKT and its downstream targets, 4EBP-1 and p70S6. Treatment with 1 μM CUDC-907 can induce cell-cycle arrest at G2–M phase and apoptosis, measured by the accumulation of cleaved PARP, activated caspase-7, p21, as well as the reduction of anti-apoptotic proteins including BCL-2, BCL-xL, and survivin in H460 cells. Treatment with CUDC-907 intravenously (50 mg/kg) can cause tumor regression in a xenograft tumor model of SU-DHL4 diffuse large B-cell lymphoma (DLBCL) while oral administration (100 mg/kg) can cause tumor stasis in RAS-mutant A549 NSCLC cell xenografts[1]. Phase 2 clinical trial of CUDC-907 for treatment of relapsed and/or refractory diffuse large B-cell lymphoma including with Myc alterations and prostate cancer are undergoing (see in https://clinicaltrials.gov/).
作用机制 CUDC-907 has the hydroxamic acid, which can chelate Zn2+ ion of HDAC, and the morpholinopyrimidine, a core structure scaffold shared by several PI3K inhibitors.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human Glioma cells (HF2303) Cytotoxicity assay 72 h Cytotoxicity against human Glioma cells (HF2303) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM 26288699
human Glioma cells (HF2381) Cytotoxicity assay 72 h Cytotoxicity against human Glioma cells (HF2381) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM 26288699
human Glioma cells (HF2476) Cytotoxicity assay 72 h Cytotoxicity against human Glioma cells (HF2476) after 72 hrs by CelltiterGlo assay, EC50=0.7 nM 26288699
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.97mL

0.39mL

0.20mL

9.83mL

1.97mL

0.98mL

19.66mL

3.93mL

1.97mL
参考文献

[1]Qian C, Lai CJ, et al. Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin Cancer Res. 2012 Aug 1;18(15):4104-13.