EZM 2302

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Chemical Structure| 1628830-21-6 同义名 : GSK3359088
CAS号 : 1628830-21-6
货号 : A345312
分子式 : C29H37ClN6O5
纯度 : 98%+
分子量 : 585.09
MDL号 : MFCD31657380
存储条件：

Pure form Keep in dark place, inert atmosphere, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 CARM1 is an arginine methyltransferase with diverse histone and non-histone substrates implicated in the regulation of cellular processes including transcriptional co-activation and RNA processing. EZM2302, also called as GSK3359088, is a CARM1 enzymatic activity inhibitor with IC50 value of 6 nM, selective to CARM1 over other histone methyltransferases. Inhibition of CARM1 by EZM2302 is synergistic with SAH. Treatment with EZM2302 <5 μM for 96h led a dose-dependent decrease in methylation of PABP1 with IC50 value of 38 nM and SmB (increased levels of SmBme0) with EC50 value of 18 nM, two well-characterized CARM1 substrates, as well as in multiple aDMA bands with IC50 value of 9nM in RPMI-8226 or NCI-H929 cells. The histone methylation at the putative CARM1 substrates H3R17 and H3R26 were also evaluated by EZM2302. EZM 2302 exhibted anti-proliferative effects on 9 of the tested multiple myeloma cell lines with various IC50 values <100 nM in the 14-day assay. EZM2302 showed oral available and appropriate pharmacokinetic properties in in vivo study. Oral administration of EZM2302, BID, for 21 days, dose-dependently inhibited tumor growth in the RPMI-8226 xenograft model SCID mice at dose of 37.5, 75, 150 and 300 mg/kg with relationship between methyl mark pharmacodynamics (PD) and tumor growth inhibition (TGI) as decrease in methylation at CARM1 substrates observed.
作用机制 EZM2302 binds the arginine pocket of CARM1 and forms a long-lived inhibitory complex with CARM1 in the presence of SAH. It may inhibit CARM1 in competitive manner.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.71mL

0.34mL

0.17mL

8.55mL

1.71mL

0.85mL

17.09mL

3.42mL

1.71mL
参考文献

[1]Drew AE, Moradei O, et al. Identification of a CARM1 Inhibitor with Potent In Vitro and In Vivo Activity in Preclinical Models of Multiple Myeloma. Sci Rep. 2017 Dec 21;7(1):17993.