MS115
MS115 is a selective PRMT5/MEP50 PROTAC degrader, with DC50 values of 17.4 nM and 11.3 nM for PRMT5 and MEP50, respectively. MS115 promotes PRMT5/MEP50 ubiquitination and degradation. MS115 shows anticancer activity against breast cancer.
(Pink: PRMT5 and MEP50 ligand (HY-173562); Blue: VHL ligand (HY-47070); Black: linker).
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- No. CAS: 3109377-60-5
- Fòrmula: C63H88FN11O13S
- Peso molecular:1258.50
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Almacenamiento:
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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Actividad biológica
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Chemical Information
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Actividad biológica
MS115 (2.1 μM; 120 min) inhibits PRMT5 methyltransferase activity in a cell-free assay with an IC50 of 2.1 μM[1].
MS115 (0.01-5 μM; 3-72 h) potently and selectively degrades PRMT5 (DC50: 17.4 nM) and MEP50 (DC50: 11.3 nM) in MDAMB468 cells in concentration- and time-dependent manners, achieving >85% maximum degradation of both proteins[1].
MS115 (0.5-5 μM; 24-72 h, with 1-2 h pretreatment for mechanism assays) mediates PRMT5/MEP50 degradation in MDAMB468 cells that requires binding to both PRMT5 and VHL, and proceeds via the ubiquitin-proteasome system[1].
MS115 (serial dilutions; 7 days) inhibits MDAMB468 cell proliferation with a gIC50 of 5.6 μM[1].
MS115 (serial dilutions; 5 days) inhibits proliferation of MDAMB453, MDAMB231, and MCF7 breast cancer cells, with potency comparable to the PRMT5 inhibitor GSKi[1].
MS115 (0.004-5 μM; 7 h-3 days) potently degrades PRMT5/MEP50 in PC-3 prostate cancer cells, showing greater efficacy than the PRMT5 degrader MS4322[1].
MS115 (0.5-5 μM; 3 days) degrades PRMT5/MEP50 in MCF10A normal breast epithelial cells and PNT2 normal prostate epithelial cells[1].
MS115 (serial dilutions; 5-6 days) degrades PRMT5/MEP50 in normal epithelial cell lines (MCF10A, PNT2) without significant cytotoxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDAMB468 triple negative breast cancer cells
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Concentration:0.01-0.5 μM (72 h degradation assay); 0.5-5 μM (24 h degradation assay); 2 μM (time-dependent degradation assay)
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Incubation Time:3-48 h (2 μM time-dependent assay); 24 h (0.5-5 μM assay); 72 h (0.01-0.5 μM assay)
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Result:Degraded PRMT5 with a DC50 of 17.4 nM and a maximum degradation (Dₘₐₓ) of 86.0 % after 72 h of treatment.
Degraded MEP50 with a DC50 of 11.3 nM and a Dₘₐₓ of 91.4 % after 72 h of treatment.
Induced time-dependent degradation, with PRMT5 degradation detectable by 6 h and MEP50 degradation detectable by 12 h of treatment with 2 μM MS115.
Reduced PRMT5 and MEP50 protein levels to near-undetectable levels at 0.5 μM, and eliminated detectable PRMT5 and MEP50 protein at 5 μM after 24 h of treatment.
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Cell Line:MDAMB468 triple negative breast cancer cells (including sgVHL and sgNTC CRISPR-modified cells)
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Concentration:0.5-5 μM (72 h degradation assay); 5 μM (24 h mechanism assay with 2 h GSKi/VHL-1 pretreatment); 5 μM (24 h mechanism assay with 1 h MG132/MLN4924 pretreatment); 0.5-5 μM (24 h sgVHL/sgNTC cell assay)
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Incubation Time:72 h (0.5-5 μM degradation assay); 24 h (5 μM mechanism assays, with 1-2 h pretreatment); 24 h (0.5-5 μM sgVHL/sgNTC cell assay)
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Result:Reduced PRMT5 and MEP50 protein levels to near-undetectable levels and inhibited sDMA levels after 72 h of treatment with 5 μM MS115.
Rescued PRMT5 and MEP50 degradation when cells were pretreated with GSKi or VHL-1, confirming dependence on PRMT5 and VHL binding.
Rescued PRMT5 and MEP50 degradation when cells were pretreated with MG132 or MLN4924, confirming the ubiquitin-proteasome system is required for degradation.
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Cell Line:MDAMB468 triple negative breast cancer cells
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Concentration:Serial dilutions
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Incubation Time:7 days
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Result:Inhibited MDAMB468 cell proliferation with a growth inhibitory IC50 (gIC50) of 5.6 μM.
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Cell Line:PC-3 prostate cancer cells
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Concentration:0.004-2.5 μM (7 h degradation assay); 0.5-5 μM (3 days degradation and sDMA assay)
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Incubation Time:7 h (0.004-2.5 μM assay); 3 days (0.5-5 μM assay)
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Result:Degraded PRMT5 and MEP50 at concentrations lower than MS4322, with detectable degradation at 0.004 μM and near-complete degradation at 2.5 μM after 7 h of treatment.
Reduced PRMT5 and MEP50 protein levels to near-undetectable levels and inhibited sDMA levels after 3 days of treatment with 5 μM MS115.
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Cell Line:MCF10A normal breast epithelial cells, PNT2 normal prostate epithelial cells
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Concentration:0.5-5 μM
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Incubation Time:3 days
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Result:Completely degraded PRMT5 and MEP50 after 3 days of treatment with 5 μM MS115, and reduced PRMT5 and MEP50 to near-undetectable levels with 0.5 μM MS115 in MCF10A cells.
Significantly reduced PRMT5 and MEP50 protein levels after 3 days of treatment with 5 μM MS115 in PNT2 cells.
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Cell Line:MCF10A normal breast epithelial cells, PNT2 normal prostate epithelial cells
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Concentration:Serial dilutions
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Incubation Time:5 days (MCF10A cells); 6 days (PNT2 cells)
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Result:Showed no significant toxicity in MCF10A cells at concentrations up to 15 μM, with cell viability remaining >100% of control at all tested concentrations.
Showed minimal toxicity in PNT2 cells, with cell viability remaining >80% of control even at the highest tested concentration.
Chemical Information
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No. CAS 3109377-60-5
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Appearance Solid
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Peso molecular 1258.50
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Fòrmula C63H88FN11O13S
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Color White to off-white
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SMILES
O=C(NC[C@@H](CN1CC2=C(CC1)C=CC=C2)O)C3=NC=NC(NC4CCN(CC4)C(CCOCCOCCOCCOCCOCCNC(C[C@H](NC([C@H]5N(C[C@@H](C5)O)C([C@H](C(C)(C)C)NC(C6(CC6)F)=O)=O)=O)C7=CC=C(C=C7)C8=C(N=CS8)C)=O)=O)=C3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Pureza y Documentación
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Ficha de datos (273 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
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- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MS115 Related Classifications
HY-173561 Related Classifications
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