MS3-123
MS3-123 is an orally active PRMT1 inhibitor (IC50 = 11.4 nM) that selectively targets the unique Cys119 residue within the SAM-binding pocket. MS3-123 covalently binds to PRMT1 through a time-dependent irreversible mechanism and exhibits high selectivity over other PRMT family members and other methyltransferases. MS3-123 inhibits breast cancer cell proliferation, migration and invasion, and induces cell cycle arrest and apoptosis. MS3-123 is useful for breast cancer research.
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- Formule: C15H24BrClN4O3S
- Masse moléculaire:455.80
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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]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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PRMT1 11.4 nM (IC50) |
PRMT3 1094.8 nM (IC50) |
PRMT4 327.1 nM (IC50) |
PRMT6 1052.4 nM (IC50) |
PRMT8 194.0 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| MCF-7/TAMR-1 | IC50 |
4.40 μM
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Exhibits antiproliferative activity against MCF-7 cells for 72 h.
Exhibits antiproliferative activity against MCF-7 cells for 72 h.
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42309962 |
| MDA-MB-231 | IC50 |
4.76 μM
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Exhibits antiproliferative activity against MDA-MB-231 cells for 72 h.
Exhibits antiproliferative activity against MDA-MB-231 cells for 72 h.
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42309962 |
MS3-123 (Compound 17zh) shows potent inhibition against PRMT1 (IC50 = 11.4 nM) with high selectivity over other PRMT family members (17 to 439 fold), labels only a limited set of off-target cysteines at 50 μM, and exhibits weak activity against multiple other methyltransferases (G9a, EHMT1, MLL1, SMYD2, SETD8, EZH2, SUV39H1) (IC50 > 10 μM), demonstrating an excellent selectivity profile[1].
MS3-123 covalently binds to PRMT1 through a time-dependent inhibition mechanism (KI = 1.52 × 104 M-1s-1)[1].
MS3-123 induces thermal stabilization of PRMT1 protein (ΔTm = 2.0°C)[1].
MS3-123 (130 μM; 1 h) covalently modifies PRMT1 at Cys119, forming a covalent complex with a mass shift of +419.2 Da[1].
The alkyne-functionalized probe of MS3-123 (100-260 μM; 1 h) effectively labels and pulls down PRMT1 protein in recombinant protein and MCF-7 cell lysates[1].
MS3-123 (0.2-3 μM; 12-84 h) concentration- and time-dependently reduces H4R3me2a and total ADMA levels in MCF-7 and MDA-MB-231 cells, with IC50 values of 0.78 μM and 0.56 μM for H4R3me2a reduction at 72 h, respectively; and significantly reduces EZH2 protein levels and AKT phosphorylation in MCF-7 cells[1].
MS3-123 (72 h) exhibits antiproliferative activity against MCF-7 and MDA-MB-231 cells, with GI50 values of 4.40 μM and 4.76 μM, respectively, and shows low toxicity against normal mammary epithelial MCF-10A cells (GI50 > 60 μM)[1].
MS3-123 (0.3-3 μM; 8-day treatment) dose-dependently inhibits colony formation in MCF-7 and MDA-MB-231 cells, with near-complete inhibition observed at 3 μM[1].
MS3-123 (0.75 μM) in combination with Gemcitabine (HY-17026) reduces the GI50 in MCF-7 cells from 3.03 μM to 0.75 μM, demonstrating a synergistic effect, with a similar trend observed in MDA-MB-231 cells[1].
MS3-123 (3-6 μM; 24 h) significantly inhibits the migration of MCF-7 and MDA-MB-231 cells[1].
MS3-123 (3-6 μM; 24 h) dose-dependently inhibits the invasion of MDA-MB-231 cells, with inhibition rates of approximately 35.0% and 57.4%, respectively[1].
MS3-123 (2-4 μM; 72 h) dose-dependently inhibits the invasion of MCF-7 cells, with inhibition rates of approximately 47.9% and 70.1%, respectively[1].
MS3-123 (6-12 μM; 24 h) dose-dependently induces S-phase cell cycle arrest in MCF-7 and MDA-MB-231 cells, characterized by a significant increase in the S-phase cell population and a corresponding decrease in the G0/G1 and G2/M phase cell populations[1].
MS3-123 (15-25 μM; 48 h) dose-dependently induces apoptosis in MCF-7 and MDA-MB-231 cells[1].
MS3-123 (1.25 μM; 0-45 min) shows a metabolic half-life of 62.1 minutes in human liver microsomes and exhibits no significant inhibition against major CYP450 enzymes (IC50 > 50 μM)[1].
MS3-123 (250 μM; 0-180 min) shows a half-life of 80.9 minutes in a GSH reactivity assay under physiological pH conditions, indicating low intrinsic reactivity[1].
MS3-123 (1 μM; 5 h) exhibits a human plasma protein binding rate of 34.7% and a free fraction of 65[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 and MDA-MB-231 cells
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Concentration:0.2, 0.4, 0.8, 1.5, and 3 μM
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Incubation Time:72 h
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Result:Results: Concentration-dependently reduced H4R3me2a and global ADMA levels; IC50 values for H4R3me2a reduction were 0.78 μM (MCF-7) and 0.56 μM (MDA-MB-231).
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Cell Line:MCF-7 cells
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Concentration:3 μM
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Incubation Time:12, 24, 48, 72, and 84 h
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Result:Time-dependently reduced H4R3me2a and global ADMA levels.
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Cell Line:MCF-7 cells
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Concentration:0.2, 0.4, 0.8, 1.5, and 3 μM
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Incubation Time:48 h
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Result:Showed little or no effect on BAF155Rme2a (PRMT4 substrate) or H3R2me2a (PRMT6 substrate) levels. Did not affect global levels of SDMA or MMA.
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Cell Line:MCF-7 and MDA-MB-231 cells
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Concentration:3 and 6 μM
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Incubation Time:24 h
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Result:Significantly inhibited cell migration at 3 and 6 μM.
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Cell Line:MDA-MB-231 cells
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Concentration:3 and 6 μM
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Incubation Time:24 h
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Result:Dose-dependently inhibited cell invasion with inhibition rates of approximately 35.0% and 57.4%, respectively.
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Cell Line:MCF-7 cells
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Concentration:2 and 4 μM
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Incubation Time:72 h
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Result:Dose-dependently inhibited cell invasion with inhibition rates of approximately 47.9% and 70.1%, respectively.
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Cell Line:MCF-7 and MDA-MB-231 cells
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Concentration:6 and 12 μM
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Incubation Time:24 h
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Result:Dose-dependently induced S-phase cell cycle arrest, accompanied by a decrease in G0/G1 and G2/M phase cell populations.
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Cell Line:MCF-7 and MDA-MB-231 cells
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Concentration:12 and 25 μM
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Incubation Time:48 h
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Result:Dose-dependently induced apoptosis.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (18-20 g) bearing subcutaneous MDA-MB-231 xenograft model (1.0 × 106 cells inoculated in PBS; administration initiated when average tumor volume reached ~100 mm3)[1].
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Dosage:100 mg/kg
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Administration:Oral gavage (i.g.); once daily; for 19 continuous days
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Result:Moderately suppressed tumor growth with a tumor growth inhibition (TGI) value of 52.3%.
Reduced ADMA and H4R3me2a protein levels in tumor tissues, confirming effective target engagement in vivo.
Caused no significant body-weight loss throughout the 19-day administration period.
Resulted in no significant differences in serum ALT, AST, or TBIL levels between the administration group and the vehicle group after 19 days of continuous administration, indicating no significant hepatotoxicity.
Caused no obvious organ damage in heart, liver, spleen, lung, or kidney based on histopathological analysis.
Chemical Information
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Masse moléculaire 455.80
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Formule C15H24BrClN4O3S
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SMILES
ClCC(NCC1=CC(S(=O)(N2CCC(CC2)N(C)C)=O)=C(N1C)Br)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MS3-123 Related Classifications
HY-184653 Related Classifications
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