CM272

Catalog No.S8812 Batch:S881201

Technical Data

Formula	C₂₈H₃₈N₄O₃
Molecular Weight	478.63	CAS No.	1846570-31-7
Solubility (25°C)*	In vitro	DMSO	96 mg/mL (200.57 mM)
		Ethanol	96 mg/mL (200.57 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

CM-272 is a novel first-in-class dual reversible inhibitor of G9a (GLP) and DNMTs with IC50 of 8 nM, 382 nM, 85 nM, 1200 nM, 2 nM for G9a, DNMT1, DNMT3A, DNMT3B, GLP, respectively. CM-272 prolongs survival in in vivo models of haematological malignancies by at least in part inducing immunogenic cell death.

Targets

G9a ^[1] (Cell-free assay)	DNMT3A ^[1] (Cell-free assay)	DNMT1 ^[1] (Cell-free assay)	DNMT3B ^[1] (Cell-free assay)
8 nM	85 nM	382 nM	1200 nM

In vitro

The GI₅₀ for CM-272 after 48 h of treatment in ALL, AML and DLBCL-derived cell lines is in the nM range and is associated with a decrease in global levels of H3K9me2 and 5mC. CM-272 inhibits cell proliferation, blocks cell cycle progression and induces apoptosis in ALL, AML and DLBCL cell lines in a dose-dependent manner. CM-272 induces IFN response and immunogenic cell death.^[1].

In vivo

CM272 therapy induces a statistically significant increase in overall survival (OS) in mice in comparison with control animals. Global H3K9me2 and 5mC levels are reduced in leukaemic cells obtained from mice engrafted with ALL-derived CEMO-1 cells after 1 week of treatment and no significant weight loss is observed in treated animals. CM272 shows dose-dependent efficacy and a dose of 2.5 mg/kg of CM272 is adequate to demonstrate the positive anti-tumour efficacy in mice engrafted with ALL-derived CEMO-1 cells.^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines ALL, AML, DLBCL, CEMO-1, LAL-CUN-2, MV4-11, OCI-AML-2, OCI-Ly3, OCI-Ly10 cell lines Concentrations -- Incubation Time 24, 48, 72 and 96h Method "100.000 cells of CEMO-1, LAL-CUN-2, MV4-11 and OCI-AML-2 cell lines are cultured at a density of 1x10⁶ cells/mL and treated for 12, 24, 48 and 72 hours with CM-272 at different concentrations (GI25, GI50 and GI75). In the case of OCI-Ly3 and OCI-Ly10, cells are treated with 100, 400 and 1000 nM for 24, 48, 72 and 96h. Cells are washed twice with phosphatebuffered saline (PBS) and resuspended in 1X Binding Buffer at a concentration of 1x10⁶ cells/mL. 1 µL of FITC Annexin V antibody and 2 µL of propidium iodide are added and incubated for 15 min at RT in the dark. Finally, 400 µL of 1X Binding Buffer are added to each tube and analyzed by flow cytometry within 1 h. "
Animal Study:^{^[1]}	Animal Models 6–8-week-old female BALB/cA−Rag2 γc mice Dosages 1, 2.5 mg/kg Administration IV

Cell Assay:^{^[1]}

Cell lines
ALL, AML, DLBCL, CEMO-1, LAL-CUN-2, MV4-11, OCI-AML-2, OCI-Ly3, OCI-Ly10 cell lines
Concentrations
--
Incubation Time
24, 48, 72 and 96h
Method
"100.000 cells of CEMO-1, LAL-CUN-2, MV4-11 and OCI-AML-2 cell lines are cultured at a density of 1x10⁶ cells/mL and treated for 12, 24, 48 and 72 hours with CM-272 at different concentrations (GI25, GI50 and GI75). In the case of OCI-Ly3 and OCI-Ly10, cells are treated with 100, 400 and 1000 nM for 24, 48, 72 and 96h. Cells are washed twice with phosphatebuffered saline (PBS) and resuspended in 1X Binding Buffer at a concentration of 1x10⁶ cells/mL. 1 µL of FITC Annexin V antibody and 2 µL of propidium iodide are added and incubated for 15 min at RT in the dark. Finally, 400 µL of 1X Binding Buffer are added to each tube and analyzed by flow cytometry within 1 h. "

Animal Study:^{^[1]}

Animal Models
6–8-week-old female BALB/cA−Rag2 γc mice
Dosages
1, 2.5 mg/kg
Administration
IV

References

[1] San José-Enériz E, et al. Nat Commun. 2017 May 26;8:15424.

Selleck's CM272 has been cited by 2 publications

Targeting G9a/DNMT1 methyltransferase activity impedes IGF2-mediated survival in hepatoblastoma [ Hepatol Commun, 2024, 8(2)e0378]	PubMed: 38285887
Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression [ Nat Med, 2019, 25(7):1073-1081]	PubMed: 31270502

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SHIPPING AND STORAGE
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