MS432
Based on 1 Customer Validation
MS432 is a potent and selective MEK1/MEK2 PRORAC degrader. MS432 specifically degrades MEK1 and MEK2 by recruiting the VHL E3 ligase, thereby potently inhibiting the phosphorylation activation of the downstream ERK pathway. MS432 can be used in research related to colorectal cancer and melanoma.
(Pink: MEK1 and MEK2 Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker (HY-W014831)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
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 : 99.72%
- CAS 番号: 2672512-44-4
- 分子式: C50H65F3IN7O6S
- 分子量:1076.06
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保管条件:
-20°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
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
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生物活性
製品説明
IC50 & Target
[1]|
MEK1 31 nM (DC50, in HT29 cells and SK-MEL-28 cells) |
MEK2 17 nM (DC50, in HT29 cells) |
MEK2 9.3 nM (DC50, in SK-MEL-28 cells) |
ERK |
VHL |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| HT-29 | DC50 |
31 nM
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MEK1 protein degradation in human HT-29 BRAFV600E mutant colorectal cancer cells assessed by Western blot analysis after 24-hour treatment.
MEK1 protein degradation in human HT-29 BRAFV600E mutant colorectal cancer cells assessed by Western blot analysis after 24-hour treatment.
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31730343 |
| HT-29 | DC50 |
17 nM
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MEK2 protein degradation in human HT-29 BRAFV600E mutant colorectal cancer cells assessed by Western blot analysis after 24-hour treatment.
MEK2 protein degradation in human HT-29 BRAFV600E mutant colorectal cancer cells assessed by Western blot analysis after 24-hour treatment.
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31730343 |
| SK-MEL-28 | DC50 |
31 nM
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MEK1 protein degradation in human SK-MEL-28 BRAFV600E mutant melanoma cells assessed by Western blot analysis after 24-hour treatment.
MEK1 protein degradation in human SK-MEL-28 BRAFV600E mutant melanoma cells assessed by Western blot analysis after 24-hour treatment.
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31730343 |
| SK-MEL-28 | DC50 |
9.3 nM
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MEK2 protein degradation in human SK-MEL-28 BRAFV600E mutant melanoma cells assessed by Western blot analysis after 24-hour treatment.
MEK2 protein degradation in human SK-MEL-28 BRAFV600E mutant melanoma cells assessed by Western blot analysis after 24-hour treatment.
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31730343 |
| HT-29 | GI50 |
130 nM
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Antiproliferative activity against human HT-29 colorectal cancer cells assessed as reduction in cell viability incubated for 3 days by MTT assay.
Antiproliferative activity against human HT-29 colorectal cancer cells assessed as reduction in cell viability incubated for 3 days by MTT assay.
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31730343 |
| SK-MEL-28 | GI50 |
83 nM
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Antiproliferative activity against human SK-MEL-28 melanoma cells assessed as reduction in cell viability incubated for 3 days by MTT assay.
Antiproliferative activity against human SK-MEL-28 melanoma cells assessed as reduction in cell viability incubated for 3 days by MTT assay.
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31730343 |
体外実験
MS432 (0.001-5 μM; 24 h) potently degrades MEK1 (DC50 = 31 nM) and MEK2 (DC50 = 17 nM) in a dose-dependent manner in HT-29 cells; it also potently degrades MEK1 (DC50 = 31 nM) and MEK2 (DC50 = 9.3 nM) in SK-MEL-28 cells, and inhibits the downstream ERK signaling pathway[1].
MS432 (0.1-0.3 μM; 2-24 h) induces time-dependent degradation of MEK1 and MEK2 and inhibits pMEK and pERK signaling in HT-29 and SK-MEL-28 cells[1].
MS432 (0.3 μM; 3-144 h) induces more sustained degradation of MEK1/2 than PD0325901 in HT-29 cells without causing a significant rebound of pERK signaling[1].
MS432 (3 days) significantly inhibits cell proliferation and survival in HT-29, SK-MEL-28, COLO 205, and UACC257 cells, with GI50 values of 130 nM and 83 nM for HT-29 and SK-MEL-28 cells, respectively[1].
MS432 (10-100 nM; 14 days) inhibits the long-term colony formation capacity of HT-29 and SK-MEL-28 cells [1].
MS432 (up to 30 μM; 2 h) inhibits purified human MEK1 and MEK2 in in vitro biochemical assays, with an IC50 of 1500 nM for MEK1 and an IC50 of 590 nM for MEK2[1].
MS432 (0.1 μM; 10 h) exhibits highly target-selective degradation of MEK1 and MEK2 in HT-29 cells, without significantly affecting other proteins in the global proteome[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:HT-29 and SK-MEL-28 cells
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Concentration:0.001, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2.5, 5 μM (HT-29); 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3 μM (SK-MEL-28)
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Incubation Time:24 h
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Result:Induced concentration-dependent degradation of MEK1 with a DC50 of 31 nM.
Induced concentration-dependent degradation of MEK2 with a DC50 of 17 nM.
Reduced over 80% of MEK1 and MEK2 protein levels at 0.5 μM.
Induced concentration-dependent degradation of MEK1 with a DC50 of 31 nM.
Induced concentration-dependent degradation of MEK2 with a DC50 of 9.3 nM.
Reduced over 90% of MEK1 and MEK2 protein levels at 0.3 μM.
Inhibited pMEK (S218/222) in a concentration-dependent manner.
Inhibited pERK (T202/Y204) in a concentration-dependent manner.
Left total ERK levels unchanged.
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Cell Line:HT-29 and SK-MEL-28 cells
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Concentration:0.1 μM, 0.3 μM
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Incubation Time:2, 4, 8, 10, 12, 24 h
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Result:Induced time-dependent degradation of MEK1/2, with significant protein elimination observed within 4-8 hours.
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Cell Line:HT-29 and SK-MEL-28 cells
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Concentration:10, 30, 100 nM
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Incubation Time:14 days
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Result:Significantly and durably inhibited the colony-forming ability of tumor cells.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | Plasma Concentration |
|---|---|---|---|---|---|
| Mice[1] | 50 mg/kg | i.p. | 0.5 h | 1400 nM | 710 nM |
体内実験
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Animal Model:Male Swiss Albino mice[1].
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Dosage:50 mg/kg (Pharmacokinetic Analysis).
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Administration:IP
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Result:Displays good plasma exposure with the maximum plasma concentration of 1,400 nM detected at 0.5 hour post dosing and plasma concentration of 710 nM at 8 hours post dosing.
化学情報
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CAS 番号 2672512-44-4
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性状 Solid
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分子量 1076.06
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分子式 C50H65F3IN7O6S
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Color White to off-white
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SMILES
O=C([C@H]1N(C([C@H](C(C)(C)C)NC(CCCCCCCCCCNCCCONC(C2=CC=C(F)C(F)=C2NC3=CC=C(I)C=C3F)=O)=O)=O)C[C@H](O)C1)N[C@H](C4=CC=C(C5=C(C)N=CS5)C=C4)C
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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, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
溶剤 & 溶解度
体外:
DMSO : 100 mg/mL (92.93 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 (protect from light, stored under nitrogen). 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 (protect from light, stored under nitrogen). 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 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.32 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
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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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
純度とドキュメンテーション
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データシート (275 KB)
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SDS (252 KB)
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- Deutsch - DE (252 KB)
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- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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 (protect from light, stored under nitrogen). 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 | 0.9293 mL | 4.6466 mL | 9.2932 mL | 23.2329 mL |
| 5 mM | 0.1859 mL | 0.9293 mL | 1.8586 mL | 4.6466 mL | |
| 10 mM | 0.0929 mL | 0.4647 mL | 0.9293 mL | 2.3233 mL | |
| 15 mM | 0.0620 mL | 0.3098 mL | 0.6195 mL | 1.5489 mL | |
| 20 mM | 0.0465 mL | 0.2323 mL | 0.4647 mL | 1.1616 mL | |
| 25 mM | 0.0372 mL | 0.1859 mL | 0.3717 mL | 0.9293 mL | |
| 30 mM | 0.0310 mL | 0.1549 mL | 0.3098 mL | 0.7744 mL | |
| 40 mM | 0.0232 mL | 0.1162 mL | 0.2323 mL | 0.5808 mL | |
| 50 mM | 0.0186 mL | 0.0929 mL | 0.1859 mL | 0.4647 mL | |
| 60 mM | 0.0155 mL | 0.0774 mL | 0.1549 mL | 0.3872 mL | |
| 80 mM | 0.0116 mL | 0.0581 mL | 0.1162 mL | 0.2904 mL |
MS432 関連分類
HY-130602 関連分類
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