CM272

CM-272 是一种首创的，有效的，选择性的，底物竞争性的且可逆的双重 G9a/DNA 甲基转移酶 (DNMTs) 抑制剂。CM-272 具有抗肿瘤活性。CM-272 抑制 G9a，DNMT1，DNMT3A，DNMT3B 和 GLP，IC50 分别为 8 nM，382 nM，85 nM，1200 nM 和 2 nM。CM-272 抑制细胞增殖并促进细胞凋亡，诱导干扰素刺激的基因和免疫原性细胞死亡。

Information

CM272 CM-272 is a novel first-in-class dual reversible inhibitor of G9a (GLP) and DNMTs with IC50 of 8 nM, 382 nM, 85 nM, 1200 nM, 2 nM for G9a , DNMT1 , DNMT3A , DNMT3B , GLP , respectively. CM-272 prolongs survival in in vivo models of haematological malignancies by at least in part inducing immunogenic cell death.

Targets

G9a (Cell-free assay); DNMT3A (Cell-free assay); DNMT1 (Cell-free assay); DNMT3B (Cell-free assay) 8 nM ;85 nM; 382 nM; 1200 nM

In vitro

The GI₅₀ for CM-272 after 48\u2009h of treatment in ALL, AML and DLBCL-derived cell lines is in the nM range and is associated with a decrease in global levels of H3K9me2 and 5mC. CM-272 inhibits cell proliferation, blocks cell cycle progression and induces apoptosis in ALL, AML and DLBCL cell lines in a dose-dependent manner. CM-272 induces IFN response and immunogenic cell death..

In vivo

CM272 therapy induces a statistically significant increase in overall survival (OS) in mice in comparison with control animals. Global H3K9me2 and 5mC levels are reduced in leukaemic cells obtained from mice engrafted with ALL-derived CEMO-1 cells after 1\u2009week of treatment and no significant weight loss is observed in treated animals. CM272 shows dose-dependent efficacy and a dose of 2.5\u2009mg/kg of CM272 is adequate to demonstrate the positive anti-tumour efficacy in mice engrafted with ALL-derived CEMO-1 cells..

Cell Research(from reference)

Cell lines：ALL, AML, DLBCL, CEMO-1, LAL-CUN-2, MV4-11, OCI-AML-2, OCI-Ly3, OCI-Ly10 cell lines 

Incubation Time：24, 48, 72 and 96h