| CAS |
No.1913252-04-6 |
| 英文名称 |
JQ-EZ-05 |
| 别名 |
JQEZ5 |
| 分子式 |
C30H38N8O2 |
| 分子量 |
542.68 |
| 溶解性 |
Soluble in DMSO ≥1mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD31619231 |
| SMILES |
CC(N1N=CC2=C(C(NCC3=C(C=C(NC3=O)C)CCC)=O)C=C(C4=CC=C(N=C4)N5CCN(C)CC5)N=C12)C |
| 靶点 |
EZH1，EZH2；Histone Methyltransferase |
| 通路 |
Epigenetics |
| 背景说明 |
JQ-EZ-05是可逆的、特异的EZH1/2抑制剂。 |
| 生物活性 |
JQEZ5 is a potent and selective EZH2 lysine methyltransferase inhibitor. JQEZ5 SAM-competitively inhibits polycomb repressive complex 2 (PRC2) with an IC50 of 80 nM. JQEZ5 has anti-tumor effects.[1] |
| In Vitro |
JQEZ5 inhibits enzymatic functionality of PRC2 with a biochemical IC50 of 80nM. JQEZ5 exhibits S-adenosyl methionine (SAM)-competitive inhibition of PRC2[1].H661 cells treated with increasing concentrations of JQEZ5 demonstrate acutely reduced levels of H3K27me3 without affecting H3K27 mono- or di-methylation. JQEZ5 suppresses the proliferation of EZH2-overexpressing H661 and H522 cells after treatment for 4 days without affecting the proliferation of cell lines that were deemed insensitive to EZH2 knockdown[1]. |
| In Vivo |
JQEZ5 (75 mg/kg; intraperitoneal injection; daily; for 3 weeks) treatment exhibits rapid and pronounced tumor regression over the three week treatment course. And H3K27me3 levels are largely reduced with treatment further confirming the on-target effect of JQEZ5 in mice[1]. |
| 动物实验 |
Tumor-bearing genetically-engineered mouse models (GEMMs) are monitored for onset of symptoms (breath distress) and then treated with JQEZ5 for three weeks (75 mg/kg IP daily). Tumors are visualized by MRI and tumor volume of the lungs is calculated using 3D Slicer. For xenograft experiments， H661 cells are dissociated into single cells， counted and resuspended at 2×106 cells per 250 μL of 1:1 media/matrigel. Eight- to 12-week-old female Foxn1nu/Foxn1nu mice are injected subcutaneously with 2×106 cells in two to three spots on the flanks. Tumors are allowed to grow to an approximate size of 200 mm3 (~10 weeks) and the mice are randomized for vehicle (n=3) or JQEZ5 administration (n=6， 75 mg/kg/d， i.p.) for 18 days. Tumor growth is measured by caliper measurements and tumor volume is calculated by standard methods[1]. |
| 数据来源文献 |
[1]. Zhang H， et al. Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer. Cancer Discov. 2016 Sep;6(9):1006-21. |
| 规格 |
5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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