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EPZ015666

现货
Catalog No.
B4989
PRMT5抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,750.00
现货
5mg
¥ 1,340.00
现货
25mg
¥ 4,180.00
现货

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Background

EPZ015666 is a potent and selective inhibitor of PRMT5 with IC50 value of 22 nM [1].

Protein arginine methyltransferase-5 (PRMT5) is an enzyme that plays an important role in many cellular processes including tumorigenesis [1].

EPZ015666 is an orally bioavailable PRMT5 inhibitor. In a competitive inhibition model, EPZ015666 inhibited PRMT5 with Ki value of 5 nM and exhibited >20000-fold selectivity over 20 other protein methyltransferases (PMTs). In MCL cell lines Z-138, Mino, Maver-1, Granta-519 and Jeko-1, EPZ015666 decreased the level of SmD3, which was a PRMT5 substrate in a concentration-dependent way. Also, EPZ015666 reduced SmD3me2s in all cell lines. The cellular thermal shift assay (CETSA) in A375 cells showed that EPZ015666 specifically bound to PRMT5. EPZ015666 showed potent antiproliferative effects with IC50 values of 96, 450 and 61-904 nM for Z-138, Maver-1 and additional MCL cell lines respectively in a concentration-dependent way [1].

In SCID mice bearing Z-138 and Maver-1 xenografts, EPZ015666 (25, 50, 100 and 200 mg/kg) showed tumor-growth inhibition (TGI) in a dose-dependent way [1].

Reference:
[1].  Chan-Penebre E, Kuplast KG, Majer CR, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol, 2015, 11(6): 432-437.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt383.44
Cas No.1616391-65-1
FormulaC20H25N5O3
Solubility≥19.17mg/mL in DMSO
Chemical Name(R)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide
SDFDownload SDF
Canonical SMILESO=C(C1=CC(NC2COC2)=NC=N1)NC[C@@H](O)CN(CC3)CC4=C3C=CC=C4
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

Z-138和Maver-1细胞

制备方法

在DMSO中的溶解度大于19.2 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0.0007 ~ 5 μM

实验结果

在Z-138和Maver-1细胞中,EPZ015666呈浓度依赖性地有效抑制细胞增殖,其IC50值分别为96 nM和450 nM。

动物实验 [1]:

动物模型

携带Z-138和Maver-1异种移植瘤的SCID小鼠

给药剂量

25、50、100和200 mg/kg;口服给药;每天2次,持续21天

实验结果

在所有指定剂量下,EPZ015666显著影响携带Z-138和Maver-1异种移植瘤的SCID小鼠的体重、体积以及肿瘤生长。在200 mg/kg的剂量下,EPZ015666抑制Z-138和Maver-1肿瘤生长,其TGI值分别为> 93%和> 70%。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Chan-Penebre E, Kuplast KG, Majer CR, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol, 2015, 11(6): 432-437.

质量控制

化学结构

EPZ015666