产品说明书

Domatinostat

Print
Chemical Structure| 910462-43-0 同义名 : 4SC-202 free base;4SC-202
CAS号 : 910462-43-0
货号 : A161236
分子式 : C23H21N5O3S
纯度 : 99%+
分子量 : 447.51
MDL号 : MFCD28155264
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 55 mg/mL(122.9 mM)，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：

2% DMSO+30% PEG 300+5% Tween 80+water 10 mg/mL

生物活性
靶点

  • HDAC10

    HDAC10, IC50:21 μM

  • HDAC3

    HDAC3, IC50:0.57 μM

  • HDAC9

    HDAC9, IC50:50 μM

  • HDAC11

    HDAC11, IC50:9.7 μM
描述 Domatinostat (4SC-202 free base) tosylate has been identified as a significant inhibitor of proliferation across both epithelial and mesenchymal urinary carcinoma (UC) cell lines, showcasing IC50 values ranging from 0.15 to 0.51 μM. Domatinostat also induces apoptosis in colorectal cancer (CRC) cells, a process which can be notably mitigated by caspase inhibitors such as z-VAD-CHO and z-DVED-CHO, suggesting its cytotoxic effects are, in part, mediated through caspase activation. Additionally, Domatinostat induces a significant G2-M phase arrest in CRC cells. Research suggests that AKT activation might play a crucial role in resistance to Domatinostat's cytotoxic effects. The cytotoxicity induced by Domatinostat is greatly enhanced under conditions of serum starvation, inhibition of AKT (via perifosine or MK-2206), or AKT1-shRNA knockdown in CRC cells. Conversely, the expression of constitutively active AKT1 (CA-AKT1) can reduce the sensitivity to Domatinostat in HT-29 cells. Remarkably, at low concentrations, Domatinostat can augment the anti-CRC activity of oxaliplatin in vitro. In the context of hepatocellular carcinoma (HCC), Domatinostat exhibits potent cytotoxic and anti-proliferative effects against both established HCC cell lines (such as HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. It activates apoptosis signal-regulating kinase 1 (ASK1), which then moves to mitochondria and physically associates with Cyp-D, indicating a pathway through which Domatinostat induces apoptosis in HCC cells.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.23mL

0.45mL

0.22mL

11.17mL

2.23mL

1.12mL

22.35mL

4.47mL

2.23mL
参考文献

[1]Pinkerneil M, et al. Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines. Target Oncol. 2016 Dec;11(6):783-798.

[2]Zhijun H, et al. Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells. Tumour Biol. 2016 Aug;37(8):10257-67.

[3]Fu M, et al. 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2016 Mar 4;471(2):267-73