CM112
CM112 is a hydrophobic tag-based PRMT1 degrader (DC50 = 0.83 μM) with pan-inhibitory activity against type I PRMTs. CM112 induces proteasome-dependent degradation of PRMT1, inhibits the methyltransferase activities of PRMT1, PRMT3, PRMT4 and PRMT6, downregulates the stability of orphan receptor TR3, thereby interfering with the non-enzymatic scaffolding function of PRMT1. CM112 suppresses clonogenicity and proliferation of tumor cells. CM112 is applicable to research related to breast cancer and non-small cell lung cancer.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Formule: C39H61N5O7
- Masse moléculaire:711.93
-
Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Activité biologique
-
Chemical Information
- Protocole
- Pureté et documentation
- Références
-
Help & FAQs
Voir tous les produits spécifiques à Isoform Histone Methyltransferase
More
Activité biologique
Description
IC50 & Target
[1]|
PRMT1 9 nM (IC50) |
PRMT1 0.83 μM (DC50) |
PRMT3 224 nM (IC50) |
PRMT4 19 nM (IC50) |
PRMT6 108 nM (IC50) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MCF7 | DC50 |
0.83 μM
|
Concentration causing 50% PRMT1 degradation in human breast cancer MCF-7 cells assessed via Western blot after 72 h incubation.
Concentration causing 50% PRMT1 degradation in human breast cancer MCF-7 cells assessed via Western blot after 72 h incubation.
|
40245820 |
In Vitro
CM112 (compound 12) (5 μM; 48 h) induces PRMT1 degradation in human breast cancer MCF-7 cells, whereas analogs with shorter carbon chains or PEG linkers do not exert this effect[1].
CM112 (0.04-10 μM; 72 h) induces concentration-dependent degradation of PRMT1 in MCF-7 human breast cancer cells, with a DC50 of 0.83 μM[1].
CM112 (0.04-10 μM; 12-96 h) induces time-dependent degradation of PRMT1 in human breast cancer MCF-7 cells, with complete elimination of PRMT1 observed at 10 μM after 96 h of treatment. Meanwhile, it inhibits the enzymatic activity of PRMT1 in a concentration-dependent manner, and reduces the levels of H4R3me2a and global ADMA within 48 h[1].
CM112 (10 μM; 12-48 h) induces proteasome-dependent degradation of PRMT1 in human MCF-7 breast cancer cells by binding to PRMT1. It acts at the post-translational level without affecting PRMT1 mRNA expression, and PRMT1 levels can recover after the compound is washed off[1].
CM112 (0.02-10 μM; 48-72 h) induces concentration-dependent degradation of PRMT1 in the human triple-negative breast cancer cell line MDA-MB-231; it also induces PRMT1 degradation in human non-small cell lung cancer cell lines H3122 and H1299, and reduces the enzymatic activity of PRMT1 in MDA-MB-231 cells[1].
CM112 (72 h) is a selective PRMT1 degrader in MCF-7 human breast cancer cells. It fails to degrade PRMT3, PRMT4 or PRMT6 at concentrations up to 10 μM, while retaining potent pan-inhibitory activity against type I PRMT enzyme activity, with IC50 values ranging from 8.9 nM to 223.9 nM[1].
CM112 (0.625-10 μM; 72 h) downregulates the stability of orphan receptor TR3 in a concentration-dependent manner in human breast cancer cell lines MCF-7 and MDA-MB-231, targeting the non-enzymatic scaffolding function of PRMT1, whereas the PRMT1 inhibitor MS023 (HY-19615) has no effect on TR3 stability[1].
CM112 (10 μM; 0-10 days) inhibits the proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, and reduces colony-forming ability and cell confluence in a time-dependent manner[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
-
Cell Line:human breast cancer MCF-7 cells
-
Concentration:5 μM
-
Incubation Time:48 h
-
Result:Induced obvious PRMT1 degradation.
-
Cell Line:human breast cancer MCF-7 cells
-
Concentration:0.04, 0.08, 0.16, 0.31, 0.62, 1.25, 2.5, 5.0, 10 μM
-
Incubation Time:72 h
-
Result:Reduced PRMT1 levels in a concentration-dependent manner, with a DC50 of 0.83 μM.
-
Cell Line:human breast cancer MCF-7 cells
-
Concentration:10 μM (time-dependent assay)
0.04, 0.15, 0.62, 2.5, 10 μM (concentration-dependent enzymatic assay) -
Incubation Time:12, 24, 48, 72, 96 h (time-dependent assay)
48 h (concentration-dependent enzymatic assay) -
Result:Caused significant PRMT1 degradation after 24 h of treatment with 10 μM, with complete degradation by 96 h.
Completely eliminated H4R3me2a after 48 h at 10 μM.
Inhibited H4R3me2a and global ADMA in a concentration-dependent manner over 48 h.
-
Cell Line:triple-negative breast cancer MDA-MB-231 cells, non-small cell lung cancer H3122 and H1299 cells
-
Concentration:0.02, 0.04, 0.08, 0.16, 0.31, 0.62, 1.25, 2.5, 5.0, 10 μM (MDA-MB-231; 72 h)
1, 5, 10 μM (H3122, H1299)
0.04, 0.15, 0.62, 2.5, 10 μM (MDA-MB-231; 48 h) -
Incubation Time:72 h (MDA-MB-231, H3122, H1299)
48 h (MDA-MB-231) -
Result:Induced concentration-dependent PRMT1 degradation in MDA-MB-231 cells, with marked reduction at submicromolar concentrations.
Induced detectable PRMT1 degradation in H3122 and H1299 cells at 10 μM.
Caused concentration-dependent inhibition of H4R3me2a and global ADMA in MDA-MB-231 cells over 48 h.
-
Cell Line:human breast cancer MCF-7 and MDA-MB-231 cells
-
Concentration:10 μM
-
Incubation Time:0, 2, 4, 6, 8, 10 days
-
Result:Visually inhibited colony formation of both cell lines in a time-dependent manner.
Exhibited potent antiproliferative effects as measured by reduced cell confluence over time.
-
Cell Line:human breast cancer MCF-7 and MDA-MB-231 cells
-
Concentration:0.625, 1.25, 2.5, 5, 10 μM
-
Incubation Time:72 h
-
Result:Downregulated TR3 protein levels in a concentration-dependent manner in both cell lines, mirroring its effect on PRMT1 levels.
Parmacokinetics
| Species | Dose | Route | AUC0-last | Cmax | Tmax | T1/2 |
|---|---|---|---|---|---|---|
| Mice[1] | 60 mg/kg | i.p. | 8732 ng·h/mL | 6937 ng/mL | 0.667 h | 1.72 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
-
Masse moléculaire 711.93
-
Formule C39H61N5O7
-
SMILES
O=C(CCOCCOCCOCCOCCOCCNC(CC12C[C@@H](C[C@H]3C2)C[C@@H](C3)C1)=O)NC4=CC=C(C5=CNC=C5CN(CCN)C)C=C4
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
-
Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
-
Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CM112 Related Classifications
HY-172769 Related Classifications
Powered by Bioz