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.
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- Fòrmula: C39H61N5O7
- Peso molecular:711.93
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
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
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MCF7 | DC50 |
0.83 μM
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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.
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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.
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Cell Line:human breast cancer MCF-7 cells
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Concentration:5 μM
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Incubation Time:48 h
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Result:Induced obvious PRMT1 degradation.
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Cell Line:human breast cancer MCF-7 cells
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Concentration:0.04, 0.08, 0.16, 0.31, 0.62, 1.25, 2.5, 5.0, 10 μM
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Incubation Time:72 h
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Result:Reduced PRMT1 levels in a concentration-dependent manner, with a DC50 of 0.83 μM.
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Cell Line:human breast cancer MCF-7 cells
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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.
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Cell Line:triple-negative breast cancer MDA-MB-231 cells, non-small cell lung cancer H3122 and H1299 cells
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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.
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Cell Line:human breast cancer MCF-7 and MDA-MB-231 cells
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Concentration:10 μM
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Incubation Time:0, 2, 4, 6, 8, 10 days
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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.
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Cell Line:human breast cancer MCF-7 and MDA-MB-231 cells
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Concentration:0.625, 1.25, 2.5, 5, 10 μM
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Incubation Time:72 h
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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
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Peso molecular 711.93
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Fòrmula C39H61N5O7
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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
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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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.
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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.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CM112 Related Classifications
HY-172769 Related Classifications
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