CM-272

CM-272 (CM272) is a novel potent, selective and reversible dual inhibitor of G9a/DNMTs with IC50 of 8 nM and 382 nM for G9a and DNMT1, respectively; also inhibits DNMT3A/3B/GLP with IC50 of 85/1,200/2 nM, respectively; inhibits cell proliferation and promotes apoptosis in different haematological neoplasias (AML, ALL and DLBCL); significantly prolongs survival of AML, ALL and DLBCL xenogeneic models.

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

Signaling Pathways >> Epigenetics >> DNA Methyltransferase

G9a:8 nM (IC50)

GLP:2 nM (IC50)

DNMT1:382 nM (IC50)

DNMT3A:85 nM (IC50)

DNMT3B:1200 nM (IC50)

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[1]. CM-272 (100-1000 nM; 24 hours; CEMO-1, MV4-11 and OCI-Ly10 cell lines) treatment blocks cell cycle progression[1]. 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[1]. 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 GI50 values of 218 nM, 269 nM and 455 nM, respectively, and is associated with a decrease in global levels of H3K9me2 and 5mC[1]. 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[1]. Cell Proliferation Assay[1] 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[1] 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[1] 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.

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

[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.