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. |
