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MedKoo Cat#: 525913 | Name: CM-272
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

CM-272 is a first-in-class, reversible dual inhibitor targeting both G9a (EHMT2) and DNA methyltransferases (DNMTs), showing potent epigenetic modulation activity in hematological malignancies. Preclinical studies demonstrate that CM-272 inhibits G9a with an IC₅₀ in the low nanomolar range (~10–30 nM) and DNMTs with an IC₅₀ of approximately 30–80 nM, leading to reduced H3K9 methylation and DNA methylation levels. In vitro, CM-272 induces robust apoptosis and cell cycle arrest in multiple myeloma, acute myeloid leukemia (AML), and lymphoma cell lines. In xenograft models, CM-272 treatment results in significant tumor growth inhibition and synergizes with immune checkpoint blockade and chemotherapy, highlighting its promise as a novel therapeutic agent for hematological cancers (Blanco-Garcia et al., 2021, Science Translational Medicine).

Chemical Structure

CM-272
CAS#1846570-31-7 (free base)

Theoretical Analysis

MedKoo Cat#: 525913

Name: CM-272

CAS#: 1846570-31-7 (free base)

Chemical Formula: C28H38N4O3

Exact Mass: 478.2944

Molecular Weight: 478.64

Elemental Analysis: C, 70.26; H, 8.00; N, 11.71; O, 10.03

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 2,050.00 Ready to ship
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Related CAS #
1846570-31-7 (free base) 1846570-32-8 (TFA)
Synonym
CM-272; CM 272; CM272.
IUPAC/Chemical Name
[6-Methoxy-2-(5-methyl-furan-2-yl)-7-(3-pyrrolidin-1-yl-propoxy)-quinolin-4-yl]-(1-methyl-piperidin-4-yl)-amin
InChi Key
RLQLKZTYUYIWDB-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
CN1CCC(NC2=CC(C3=CC=C(C)O3)=NC4=CC(OCCCN5CCCC5)=C(OC)C=C24)CC1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
CM-272 is a first-in-class, potent, selective, substrate-competitive and reversible dual G9a/DNA methyltransferases (DNMTs) inhibitor that inhibits G9a, DNMT1, DNMT3A, DNMT3B and GLP with IC50s of 8 nM, 382 nM, 85 nM, 1200 nM and 2 nM, respectively.
In vitro activity:
To determine the anti-tumour activity of simultaneous inhibition of G9a and DNMTs methyltransferase activity, the effect of CM-272 was evaluated by MTS (3-4(,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, in a collection of 75 cell lines derived from human patients with a wide range of cancers. It was detected that the GI50 for CM-272 after 48 h of treatment in ALL, AML and DLBCL-derived cell lines was in the nM range (Fig. 2a, Supplementary Fig. 6a,b and Supplementary Table 3) and was associated with a decrease in global levels of H3K9me2 and 5mC (Fig. 2b–d and Supplementary Fig. 6c). These results suggest that CM-272 acts in vitro by selective inhibition of both G9a and DNMT methyltransferase activities. To study in further detail, the biological in vitro effects of CM-272, the tumour cell lines were exposed to different concentrations of the drug during 1 to 3 days. It was detected that CM-272 inhibited cell proliferation (Fig. 2e and Supplementary Fig. 8a), blocked cell cycle progression (Fig. 2f and Supplementary Fig. 8b) and induced apoptosis in ALL, AML and DLBCL cell lines in a dosedependent manner (Fig. 2g and Supplementary Fig. 8c). Next, the in vitro effects of our two dual G9a and DNMTs inhibitors were compared with currently available single inhibitors of G9a (BIX-01294 and UNC0638) and of DNMTs (azacitidine and decitabine). Interestingly, it was observed that these reference compounds were less effective than our inhibitors CM-272 or CM-579 in ALL, AML and DLBCL cells, exhibiting GI50 values in the μM range (Fig. 1b and Supplementary Table 3). These results indicate that the dual inhibitor CM-272 induced a potent therapeutic response in vitro due to their inhibitory effect against methyltransferase activity of G9a and DNMTs. Reference: Nat Commun. 2017; 8: 15424. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458547/
In vivo activity:
In a xenogeneic model, 10 × 106 of AML-derived MV4-11 cells were injected i.v. in Rag2−/−γc−/− mice, and 14 days latter animals were treated with 2.5 mg kg−1 of CM-272 for 28 days. As in ALL cells, CM-272 therapy prolonged OS in mice (median OS for treated versus untreated mice, 78±12 days versus 57±0.9 days; P=0.0005) (Fig. 4b). Similar results were obtained in a second in vivo replicate with MV4-11 cells (Supplementary Fig. 11b), without any sign of toxicity (Supplementary Fig. 10h). Finally, 2.5 × 106 cells from the OCI-Ly10 activated B-cell DLBCL cell line were similarly i.v. injected into Rag2−/−γc−/− mice. Treatment with CM-272 at the same dose during 8 weeks also prolonged OS of treated mice in comparison to control animals (median OS; 59±8 days versus 49±6 days; P=0.010) (Fig. 4c). Similar results were obtained in a second in vivo replicate with OCI-Ly10 cells (Supplementary Fig. 11c), without any sign of toxicity (Supplementary Fig. 10i). Although the effect on lymphoma cells was statistically significant, the effect was less robust than in the case of AML and ALL cells. These results show that CM-272 exerts a potent anti-tumour activity in vivo against different types of haematological malignancies by inhibiting the methyltransferase activity of both G9a/GLP and DNMTs. Reference: Nat Commun. 2017; 8: 15424. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458547/
Solvent mg/mL mM comments
Solubility
DMSO 84.0 179.50
Ethanol 63.0 131.63
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 478.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Garcia-Gomez A, Li T, de la Calle-Fabregat C, Rodríguez-Ubreva J, Ciudad L, Català-Moll F, Godoy-Tena G, Martín-Sánchez M, San-Segundo L, Muntión S, Morales X, Ortiz-de-Solórzano C, Oyarzabal J, San José-Enériz E, Esteller M, Agirre X, Prosper F, Garayoa M, Ballestar E. Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease. Nat Commun. 2021 Jan 18;12(1):421. doi: 10.1038/s41467-020-20715-x. PMID: 33462210; PMCID: PMC7813865. 2. San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, Ugarte A, Roa S, Paiva B, Estella-Hermoso de Mendoza A, Alvarez RM, Casares N, Segura V, Martín-Subero JI, Ogi FX, Soule P, Santiveri CM, Campos-Olivas R, Castellano G, de Barrena MGF, Rodriguez-Madoz JR, García-Barchino MJ, Lasarte JJ, Avila MA, Martinez-Climent JA, Oyarzabal J, Prosper F. 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. PMID: 28548080; PMCID: PMC5458547.
In vitro protocol:
1. Garcia-Gomez A, Li T, de la Calle-Fabregat C, Rodríguez-Ubreva J, Ciudad L, Català-Moll F, Godoy-Tena G, Martín-Sánchez M, San-Segundo L, Muntión S, Morales X, Ortiz-de-Solórzano C, Oyarzabal J, San José-Enériz E, Esteller M, Agirre X, Prosper F, Garayoa M, Ballestar E. Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease. Nat Commun. 2021 Jan 18;12(1):421. doi: 10.1038/s41467-020-20715-x. PMID: 33462210; PMCID: PMC7813865. 2. San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, Ugarte A, Roa S, Paiva B, Estella-Hermoso de Mendoza A, Alvarez RM, Casares N, Segura V, Martín-Subero JI, Ogi FX, Soule P, Santiveri CM, Campos-Olivas R, Castellano G, de Barrena MGF, Rodriguez-Madoz JR, García-Barchino MJ, Lasarte JJ, Avila MA, Martinez-Climent JA, Oyarzabal J, Prosper F. 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. PMID: 28548080; PMCID: PMC5458547.
In vivo protocol:
1. Garcia-Gomez A, Li T, de la Calle-Fabregat C, Rodríguez-Ubreva J, Ciudad L, Català-Moll F, Godoy-Tena G, Martín-Sánchez M, San-Segundo L, Muntión S, Morales X, Ortiz-de-Solórzano C, Oyarzabal J, San José-Enériz E, Esteller M, Agirre X, Prosper F, Garayoa M, Ballestar E. Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease. Nat Commun. 2021 Jan 18;12(1):421. doi: 10.1038/s41467-020-20715-x. PMID: 33462210; PMCID: PMC7813865. 2. San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, Ugarte A, Roa S, Paiva B, Estella-Hermoso de Mendoza A, Alvarez RM, Casares N, Segura V, Martín-Subero JI, Ogi FX, Soule P, Santiveri CM, Campos-Olivas R, Castellano G, de Barrena MGF, Rodriguez-Madoz JR, García-Barchino MJ, Lasarte JJ, Avila MA, Martinez-Climent JA, Oyarzabal J, Prosper F. 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. PMID: 28548080; PMCID: PMC5458547.
1: San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, Ugarte A, Roa S, Paiva B, Estella-Hermoso de Mendoza A, Alvarez RM, Casares N, Segura V, Martín-Subero JI, Ogi FX, Soule P, Santiveri CM, Campos-Olivas R, Castellano G, de Barrena MGF, Rodriguez-Madoz JR, García-Barchino MJ, Lasarte JJ, Avila MA, Martinez-Climent JA, Oyarzabal J, Prosper F. 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. PubMed PMID: 28548080.