CM-272

CM-272 is a first-in-class, potent, selective, substrate-competitive and reversible dual G9a/DNA methyltransferases (DNMTs) inhibitor. 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. Anti-tumour Activity.

Product information

CAS Number: 1846570-31-7

Molecular Weight: 478.63

Formula: C28H38N4O3

Chemical Name: 6-methoxy-2-(5-methylfuran-2-yl)-N-(1-methylpiperidin-4-yl)-7-[3-(pyrrolidin-1-yl)propoxy]quinolin-4-amine

Smiles: CN1CCC(CC1)NC1=CC(=NC2=CC(OCCCN3CCCC3)=C(C=C21)OC)C1=CC=C(C)O1

InChiKey: RLQLKZTYUYIWDB-UHFFFAOYSA-N

InChi: InChI=1S/C28H38N4O3/c1-20-7-8-26(35-20)25-18-23(29-21-9-14-31(2)15-10-21)22-17-27(33-3)28(19-24(22)30-25)34-16-6-13-32-11-4-5-12-32/h7-8,17-19,21H,4-6,9-16H2,1-3H3,(H,29,30)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 125 mg/mL (261.16 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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 GI50 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 tumour cells.

In Vivo:

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.

References:

1. San Jose-Eneriz 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.

Products are for research use only. Not for human use.