MS1129
Based on 1 Customer Validation
MS1129 is a DNMT degrader that induces proteasomal degradation of DNMT1, DNMT3A and DNMT3B proteins. MS1129 upregulates TRAIL, DR4 and DR5 proteins, downregulates the decoy receptor DcR2, and activates TRAIL-dependent apoptosis via the HIF-1/2 and Caspase-10 pathways. MS1129 is applicable to the research of VHL-deficient clear cell renal cell carcinoma.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.46%
- 分子式: C30H24N4O3
- 分子量:488.54
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 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
製品説明
IC50 & Target
[1]|
DNMT1 |
DNMT3A |
DNMT3B |
Caspase-10 |
Caspase-3 |
Caspase-7 |
体外実験
MS1129 (2 μM; 3 days) induces robust apoptosis in parental VHL-deficient RCC10 clear cell renal cell carcinoma cells, and this effect is dependent on the expression of HIF-1α/2α[1].
MS1129 inhibits the viability of parental VHL-deficient RCC10 clear cell renal cell carcinoma (ccRCC) cells with an IC50 of 1.3 μM, while its potency decreases in HIF-1α/2α double knockout (DKO) RCC10 cells (IC50 = 3.2 μM)[1].
MS1129 (2 μM; 0-48 h) induces time-dependent proteasomal degradation of DNMT1, DNMT3A and DNMT3B proteins in RCC10 clear cell renal cell carcinoma cells, with the maximum degradation level reached at 48 h[1].
MS1129 (1-3 μM; 2 days) induces apoptosis in RCC10 clear cell renal cell carcinoma (ccRCC) cells by activating caspase-3, caspase-7 and PARP1, while the pan-caspase inhibitor Z-VAD-FMK (HY-16658B) partially inhibits this effect[1].
MS1129 (2 μM; 2 days) activates the TRAIL death receptor signaling pathway in RCC10 ccRCC cells by upregulating TRAIL, DR4 and DR5, downregulating DcR2, and inducing caspase-10 cleavage[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:Parental VHL-deficient RCC10 ccRCC cells, HIF-1α/2α-DKO RCC10 ccRCC cells
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Concentration:2 μM
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Incubation Time:3 days
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Result:Induced robust cell death in parental RCC10 cells, resulting in ~80% PI-positive cells.
Showed minimal PI-positive cells in HIF-1α/2α-DKO RCC10 cells, comparable to vehicle controls.
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Cell Line:RCC10 ccRCC cells
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Concentration:2 μM (MS1129); 10 μM MG132 (co-treatment); 2 μM MG262 (co-treatment)
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Incubation Time:0, 12, 18, 24, 36, 48 h (MS1129); 6 h (MG132 after 36 h MS1129); 2 h (MG262 after 36 h MS1129)
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Result:Induced time-dependent proteasomal degradation of DNMT1, DNMT3A, and DNMT3B proteins, with degradation detectable as early as 12 h and progressing through 48 h.
Blocked degradation of DNMT proteins when co-treated with proteasome inhibitors MG132 or MG262.
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Cell Line:RCC10 ccRCC cells
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Concentration:1-3 μM (MS1129); 2 μM (MS1129 with Z-VAD-FMK); 20 μM Z-VAD-FMK (pre-treatment)
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Incubation Time:2 days (1-3 μM MS1129); 3 days (2 μM MS1129 with Z-VAD-FMK); 30 min (Z-VAD-FMK pre-treatment)
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Result:Induced dose-dependent increases in cleaved caspase-3, cleaved caspase-7, and cleaved PARP1 levels in RCC10 cells after 2 days of treatment.
Reduced PI-positive cells from ~80% to ~30% when cells were pre-treated with 20 μM Z-VAD-FMK prior to 2 μM MS1129 treatment for 3 days.
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Cell Line:RCC10 ccRCC cells
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Concentration:2 μM
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Incubation Time:2 days
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Result:Upregulated protein levels of TRAIL, DR4, and DR5.
Downregulated protein levels of decoy receptor DcR2.
Induced cleavage of procaspase-10 to active cleaved caspase-10.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | Vz/F | CL/F | MRT |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.p. | 294 min | 90 min | 618 ng/mL | 178978 min·ng/mL | 11359 mL | 26.8 mL/min | 352 min |
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (male, 6-8 weeks old, subcutaneous implantation of 786-O cells)[1]
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Dosage:5 mg/kg
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Administration:i.p.; daily; 10 days
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Result:Reduced tumor volume relative to vehicle controls.
Lowered tumor weights significantly compared to vehicle-treated mice.
Remained stable in mouse body weight throughout treatment.
化学情報
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性状 Solid
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分子量 488.54
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分子式 C30H24N4O3
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Color Light yellow to yellow
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SMILES
COC1=C(C=CC=C1)C(NC2=CC=C(C=C2)NC(C3=CC=C(C=C3)NC4=CC=NC5=C4C=CC=C5)=O)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 50 mg/mL (102.35 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. 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. 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)
体内:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (5.12 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
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Detection of Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
純度とドキュメンテーション
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データシート (278 KB)
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取扱説明書 (2659 KB)
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. 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 | 2.0469 mL | 10.2346 mL | 20.4692 mL | 51.1729 mL |
| 5 mM | 0.4094 mL | 2.0469 mL | 4.0938 mL | 10.2346 mL | |
| 10 mM | 0.2047 mL | 1.0235 mL | 2.0469 mL | 5.1173 mL | |
| 15 mM | 0.1365 mL | 0.6823 mL | 1.3646 mL | 3.4115 mL | |
| 20 mM | 0.1023 mL | 0.5117 mL | 1.0235 mL | 2.5586 mL | |
| 25 mM | 0.0819 mL | 0.4094 mL | 0.8188 mL | 2.0469 mL | |
| 30 mM | 0.0682 mL | 0.3412 mL | 0.6823 mL | 1.7058 mL | |
| 40 mM | 0.0512 mL | 0.2559 mL | 0.5117 mL | 1.2793 mL | |
| 50 mM | 0.0409 mL | 0.2047 mL | 0.4094 mL | 1.0235 mL | |
| 60 mM | 0.0341 mL | 0.1706 mL | 0.3412 mL | 0.8529 mL | |
| 80 mM | 0.0256 mL | 0.1279 mL | 0.2559 mL | 0.6397 mL | |
| 100 mM | 0.0205 mL | 0.1023 mL | 0.2047 mL | 0.5117 mL |
MS1129 関連分類
HY-181955 関連分類
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