MS115 TFA
MS115 TFA is a selective PRMT5/MEP50 PROTAC degrader, with DC50 values of 17.4 nM and 11.3 nM for PRMT5 and MEP50, respectively. MS115 TFA promotes PRMT5/MEP50 ubiquitination and degradation. MS115 TFA shows anticancer activity against breast cancer.
(Pink: PRMT5 and MEP50 ligand (HY-173562); Blue: VHL ligand (HY-47070); Black: linker).
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- CAS 番号: 3109377-61-6
- 分子式: C65H89F4N11O15S
- 分子量:1372.53
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保管条件:
-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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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
MS115 (2.1 μM; 120 min) TFA 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) TFA 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) TFA 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) TFA inhibits MDAMB468 cell proliferation with a gIC50 of 5.6 μM[1].
MS115 (serial dilutions; 5 days) TFA 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) TFA 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) TFA degrades PRMT5/MEP50 in MCF10A normal breast epithelial cells and PNT2 normal prostate epithelial cells[1].
MS115 (serial dilutions; 5-6 days) TFA 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.
| Species | Dose | Route | Cmax | Plasma Concentration |
|---|---|---|---|---|
| Mice[1] | 50 mg/kg | i.p. | 17.5 μM | >200 nM |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Swiss albino (male)[1]
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Dosage:50 mg/kg
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Administration:i.p.; single dose
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Result:Achieved a peak plasma concentration (Cmax) of 17.5 μM at 0.5 hours post-administration.
Remained above 200 nM for up to 8 hours post-administration.
化学情報
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CAS 番号 3109377-61-6
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性状 Solid
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分子量 1372.53
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分子式 C65H89F4N11O15S
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Color White to off-white
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SMILES
OC(C(F)(F)F)=O.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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-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)
溶剤 & 溶解度
DMSO : 100 mg/mL (72.86 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.7286 mL | 3.6429 mL | 7.2858 mL | 18.2145 mL |
| 5 mM | 0.1457 mL | 0.7286 mL | 1.4572 mL | 3.6429 mL | |
| 10 mM | 0.0729 mL | 0.3643 mL | 0.7286 mL | 1.8215 mL | |
| 15 mM | 0.0486 mL | 0.2429 mL | 0.4857 mL | 1.2143 mL | |
| 20 mM | 0.0364 mL | 0.1821 mL | 0.3643 mL | 0.9107 mL | |
| 25 mM | 0.0291 mL | 0.1457 mL | 0.2914 mL | 0.7286 mL | |
| 30 mM | 0.0243 mL | 0.1214 mL | 0.2429 mL | 0.6072 mL | |
| 40 mM | 0.0182 mL | 0.0911 mL | 0.1821 mL | 0.4554 mL | |
| 50 mM | 0.0146 mL | 0.0729 mL | 0.1457 mL | 0.3643 mL | |
| 60 mM | 0.0121 mL | 0.0607 mL | 0.1214 mL | 0.3036 mL |
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