ChemicalBook CAS DataBase List 1846570-31-7

1846570-31-7

Name	CM-272
CAS	1846570-31-7
Molecular Formula	C28H38N4O3
MDL Number	MFCD31812316
Molecular Weight	478.63
MOL File	1846570-31-7.mol

Chemical Properties

Boiling point	631.9±55.0 °C(Predicted)
density	1.164±0.06 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO:84.0(Max Conc. mg/mL);179.5(Max Conc. mM) Ethanol:63.0(Max Conc. mg/mL);131.63(Max Conc. mM)
form	A crystalline solid
pka	10.09±0.20(Predicted)
color	Light brown to brown

Safety Data

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H302-H315-H319-H335
Precautionary statements	P261-P280-P301+P312-P302+P352-P305+P351+P338

Hazard Information

Uses

CM-272 is a first-in-class, potent, selective, substrate-competitive and reversible dual G9a/DNA methyltransferases (DNMTs) inhibitor with antitumor activities. CM-272 inhibits G9a, DNMT1, DNMT3A, DNMT3B and GLP with IC50s of 8 nM, 382 nM, 85 nM, 1200 nM and 2 nM, respectively. CM-272 inhibits cell proliferation and promotes apoptosis, inducing IFN-stimulated genes and immunogenic cell death[1].

Biological Activity

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

in vitro

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 tumou r 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:
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

< tr>

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-dep endent manner.

in vivo

CM-272 (2.5 mg/kg; injection; daily; for 28 days; female Rag2 intravenous ^?/? 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.

target

< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> DNMT1
(Cell-free assay)

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

IC 50

G9a: 8 nM (IC₅₀); EHMT1/GLP/KMT1D: 2 nM (IC₅₀); DNMT1: 382 nM (IC₅₀); DNMT3A: 85 nM (IC₅₀); DNMT3B: 1200 nM (IC₅₀)

storage

Store at -20°C

References

[1] San José-Enériz E, et al. Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies. Nat Commun. 2017 May 26;8:15424. DOI:10.1038/ncomms15424

Spectrum Detail

Supplier

Bide Pharmatech Ltd.

Telephone400-164-7117 18317119277

Websitehttp://www.bidepharm.com

Shanghai Macklin Biochemical Co.,Ltd.

Telephone15221275939 15221275939

Websitehttp://www.macklin.cn

Shanghai Lollane Biological Technology Co.,Ltd.

Telephone021-52996696，15000506266 15000506266

Websitehttp://www.bioll.com

Shanghai Beckham Medical Technology Co., Ltd

Telephone 13816613772

Websitehttps://www.chemicalbook.com/ShowSupplierProductsList16976/0_EN.htm

Shanghai EFE Biological Technology Co., Ltd.

Telephone021-65675885 18964387627

Websitehttp://www.efebio.com

Shanghai YuanYe Biotechnology Co., Ltd.

Telephone 15026964105

Websitehttps://www.shyuanye.com

ShangHai Biochempartner Co.,Ltd

Telephone177-54423994 17754423994

Websitehttps://www.biochempartner.com

Shanghai SuperLan Chemcial Technique Centre

Telephone0-2022843681 15618226720

Websitehttps://www.chemicalbook.com/ShowSupplierProductsList19886/0_EN.htm

Twochem Co.Ltd.

Telephone021-58111628 15800915896

Websitehttp://cn.twochem.com

Shanghai Tube Pharmaceutical Co., Ltd.

Telephone021-54338626 18017892860

Websitehttp://www.tubepharm.com

Shanghai Jizhi Biochemical Technology Co. Ltd.

Telephone021-4009004166/18616739031 18616739031

Websitehttp://www.acmec-e.com/

Zhejiang J&C Biological Technology Co.,Limited

Telephone+1-2135480471

Websitehttps://www.sarms4muscle.com

HANGZHOU CLAP TECHNOLOGY CO.,LTD

Telephone86-571-88216897,88216896 13588875226

Websitehttp://www.hzclap.com/en/

Changzhou Chenhong Biotechnology Co., Ltd.

Telephone+86-0519-85788828 +86-13775037613

Websitehttp://www.chemrenblock.com/

ChemeGen(Shanghai) Biotechnology Co.,Ltd.

Telephone 18818260767

Websitehttp://www.chemegen.com

ShangHai ChuanQian Chemcial Technique Centre

Telephone 15869524721

Websitehttps://www.chemicalbook.com/ShowSupplierProductsList68594/0_EN.htm

cjbscvictory

Telephone13348960310 13348960310

Websitehttps://www.weikeqi-biotech.com/

Shanghai Sunway Pharmaceutical Technology Co.,Ltd.

Telephone13611835272 13611835272

Websitehttp://www.sunwaypharm.cn/

1of4

Related Products

Send Inquriy