1846570-31-7

中文名称化合物CM-272

英文名称 CM-272

CAS 1846570-31-7

分子式 C28H38N4O3

分子量 478.63

MOL 文件 1846570-31-7.mol

更新日期 2024/05/23 20:39:44

1846570-31-7 结构式

基本信息物理化学性质安全数据常见问题列表

基本信息

中文别名

化合物CM-272
6-甲氧基-2-(5-甲基呋喃-2-基)-N-(1-甲基哌啶-4-基)-7-(3-(吡咯烷-1-基)丙氧基)喹啉-4-胺

英文别名

CM-272
CM-272
CM 272
CM272
6-Methoxy-2-(5-methylfuran-2-yl)-N-(1-methylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-amine
4-Quinolinamine, 6-methoxy-2-(5-methyl-2-furanyl)-N-(1-methyl-4-piperidinyl)-7-[3-(1-pyrrolidinyl)propoxy]-

物理化学性质

沸点631.9±55.0 °C(Predicted)

密度1.164±0.06 g/cm3(Predicted)

储存条件-20°C储存

溶解度DMSO:84.0(Max Conc. mg/mL);179.5(Max Conc. mM)
Ethanol:63.0(Max Conc. mg/mL);131.63(Max Conc. mM)

酸度系数(pKa)10.09±0.20(Predicted)

形态结晶固体

安全数据

危险性符号(GHS)

GHS07

警示词警告

危险性描述H302-H315-H319-H335

防范说明P261-P280-P301+P312-P302+P352-P305+P351+P338

常见问题列表

生物活性

CM272是新型、一流的G9a (GLP) 和 DNMTs双重可逆抑制剂，对G9a, DNMT1, DNMT3A, DNMT3B, GLP的IC50值分别为8 nM, 382 nM, 85 nM, 1200 nM, 2 nM。CM272通过至少部分诱导免疫原性细胞死亡，延长了血液系统恶性肿瘤体内模型的存活时间。

靶点

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

体外研究

CM-272 (100-1000 nM; 12-72 hours; CEMO-1, MV4-11 and OCI-Ly10 cell lines) treatment inhibits cell proliferation in a dose- and time-dependent manner.
CM-272 (100-1000 nM; 24 hours; CEMO-1, MV4-11 and OCI-Ly10 cell lines) treatment blocks cell cycle progression.
CM-272 (100-1000 nM; 12-72 hours; CEMO-1, MV4-11 and OCI-Ly10 cell lines) treatment induces apoptosis in ALL, AML and DLBCL cell lines in a dose- and time-dependent manner.
CM-272 after 48 h of treatment CEMO-1 acute lymphoblastic leukaemia (ALL) cell line, MV4-11 acute myeloid leukaemia (AML) cell line and OCI-Ly10 diffuse large B-cell lymphoma (DLBCL) cell line, the GI ₅₀ values of 218 nM, 269 nM and 455 nM, respectively, and is associated with a decrease in global levels of H3K9me2 and 5mC.
The therapeutic activity of CM-272 relies on the early activation of the type I IFN response in tumour cells, potentially leading to the induction of cell autonomous immunogenic death in tumour cells.

Cell Proliferation Assay

Cell Line:	CEMO-1, MV4-11 and OCI-Ly10 cell lines
Concentration:	125 nM, 250 nM, 500 nM (CEMO-1 cells); 135 nM, 270 nM, 540 nM (MV4-11 cells); 100 nM, 400 nM, 1000 nM (OCI-Ly10 cells)
Incubation Time:	12 hours, 24 hours, 48 hours and 72 hours
Result:	Inhibited cell proliferation in a dose- and time-dependent manner.

Cell Cycle Analysis

Cell Line:	CEMO-1, MV4-11 and OCI-Ly10 cell lines
Concentration:	125 nM, 250 nM, 500 nM (CEMO-1 cells); 135 nM, 270 nM, 540 nM (MV4-11 cells); 100 nM, 400 nM, 1000 nM (OCI-Ly10 cells)
Incubation Time:	24 hours
Result:	Blocked cell cycle progression.

Apoptosis Analysis

Cell Line:	CEMO-1, MV4-11 and OCI-Ly10 cell lines
Concentration:	125 nM, 250 nM, 500 nM (CEMO-1 cells); 135 nM, 270 nM, 540 nM (MV4-11 cells); 100 nM, 400 nM, 1000 nM (OCI-Ly10 cells)
Incubation Time:	12 hours, 24 hours, 48 hours and 72 hours
Result:	Induced apoptosis in ALL, AML and DLBCL cell lines in a dose- and time-dependent manner.

体内研究

CM-272 (2.5 mg/kg; intravenous injection; daily; for 28 days; female Rag2 ^−/− γc ^−/− mice) treatment significantly prolongs survival of CEMO-1 cells xenogeneic models.

Animal Model:	Female BALB/Ca-Rag2 ^−/− γc ^−/− mice (6–8-week-old) with CEMO-1 cells
Dosage:	2.5 mg/kg
Administration:	Intravenous injection; daily; for 28 days
Result:	Induced a statistically significant increase in overall survival (OS) in mice.