| Identification | Back Directory | [Name]
CM-272 | [CAS]
1846570-31-7 | [Synonyms]
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]- | [Molecular Formula]
C28H38N4O3 | [MDL Number]
MFCD31812316 | [MOL File]
1846570-31-7.mol | [Molecular Weight]
478.63 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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 | 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 | < tr> 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]
| Target | Value | G9a
(Cell-free assay) | 8 nM | DNMT3A
(Cell-free assay) | 85 nM | < td style="border-bottom: 1px dotted #ccc;padding: 5px;"> DNMT1
(Cell-free assay) 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 |
|
| Company Name: |
BOC Sciences
|
| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
| Company Name: |
Twochem Co.Ltd.
|
| Tel: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
|