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EPZ015666
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
EPZ015666图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
2mg电议
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
EPZ015666 (GSK3235025) 是一种口服有效的 PRMT5 抑制剂,IC50 为 22 nM。

Cell lines

Z-138 and Maver-1 cells

Preparation method

The solubility of this compound in DMSO is > 19.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

0.0007 ~ 5 μM

Applications

In Z-138 and Maver-1 cells, EPZ015666 potently inhibited cell proliferation in a concentration-dependent manner, with the IC50 values of 96 nM and 450 nM, respectively.

Animal models

SCID mice bearing Z-138 and Maver-1 xenografts

Dosage form

25, 50, 100 and 200 mg/kg; p.o.; b.i.d., for 21 days

Applications

EPZ015666, at all indicated doses, significantly affected weight, volume and tumor growth of SCID mice bearing Z-138 and Maver-1 xenografts. At the dose of 200 mg/kg, EPZ015666 induced tumor stasis in Z-138 cells and Maver-1 cells, with the TGI values of > 93% and > 70%, respectively.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

产品描述

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.