EZM 2302

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

EZM 2302 (EZM2302, GSK 3359088) 是一种有效的、选择性的、口服的精氨酸甲基转移酶 CARM1 抑制剂，IC50 为 6 nM。

EZM 2302 (EZM2302, GSK 3359088)?is a potent, selective, orally available arginine methyltransferase CARM1 inhibitor with IC50 of 6 nM, with broad selectivity against other HMTases; demonstrates in vitro anti-proliferative activity consistent with specific methyl mark inhibition with IC50 of <100 nM in 9/15 multiple myeloma cell lines, decreases methylation of PABP1 (IC50?=38 nM) and SmB (IC50=18 nM); displays dose-dependent inhibition of CARM1 substrate methylation in vivo, and induces growth inhibition of human multiple myeloma tumor xenografts in mice.

EZM 2302 binds to CARM1 and is a selective inhibitor of CARM1 activity (IC50=6?nM) with broad selectivity against other histone methyltransferases. Treatment of MM cell lines with EZM 2302 leads to inhibition of PABP1 and SMB methylation and cell stasis with IC50 values in the nanomolar range (9, 31 nM, respectively). EZM 2302 inhibits the in vitro proliferation of multiple hematopoietic cell lines, with day 14 IC50 values of less than 100?nM in 9 of 15 cell lines.

EZM 2302 is stable in human hepatocytes (CL<3?mL/min/kg), and moderately binds to human, mouse and rat plasma proteins with a mean fraction unbound of 0.66, 0.46 and 0.74, respectively. In mouse and rat, the plasma clearance (CL) is 43 and 91?mL/min/kg, respectively. EZM 2302 shows dose-dependent exposure and tumor growth inhibition (TGI) after 21 days in the RPMI-8226 xenograft model. Tumors in all EZM 2302 dose groups measured on day 21 show significant decreases in tumor growth compared to vehicle.

GSK 3359088 | GSK3359088 | EZM2302

Chromatin/Epigenetic

HMTase

HMTase

Cancer

——

1628830-21-6

585.102

C29H37ClN6O5

>98% (HPLC)

100 mM in DMSO

O=C(N(CC1)CCC21CN(C3=NC(C4=CC(OC[C@H](O)CNC)=CC=C4Cl)=NC(C5=C(C)ON=C5C)=C3C)C2)OC

methyl (R)-2-(2-(2-chloro-5-(2-hydroxy-3-(methylamino)propoxy)phenyl)-6-(3,5-dimethylisoxazol-4-yl)-5-methylpyrimidin-4-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

(-20℃)

With Ice Pack

≥ 2 years