MS4078
Based on 4 publication(s) in Google Scholar
MS4078 is a ALK PROTAC degrader with a DC50 of 11 nM in SU-DHL-1 cells and a DC50 of 59 nM in NCI-H2228 cells, and its Kd value for ALK binding is 19 nM. MS4078 induces ALK degradation via the ubiquitin-proteasome pathway by recruiting cereblon, and inhibits the phosphorylation of ALK and STAT3, thereby suppressing cancer cell proliferation. MS4078 is applicable for the research of non-small cell lung cancer and anaplastic large cell non-Hodgkin's lymphoma.
(Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-15656); Blue: Cereblon ligand (HY-14658); Black: linker).
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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: 99.72%
- CAS 番号: 2229036-62-6
- 分子式: C45H52ClN9O8S
- 分子量:914.47
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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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
MedChemExpress（MCE）の使用を引用している文献 MS4078
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生物活性
製品説明
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ALK 11 nM (DC50, SU-DHL-1 cells) |
ALK 59 nM (DC50, NCI-H2228 cells) |
ALK 19 nM (Kd) |
p-STAT3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SU-DHL-1 | DC50 |
11 nM
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Degradation of ALK fusion proteins in human SU-DHL-1 lymphoma cells.
Degradation of ALK fusion proteins in human SU-DHL-1 lymphoma cells.
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36986673 |
| NCI-H2228 | DC50 |
59 nM
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Degradation of ALK fusion proteins in human NCI-H2228 lung cancer cells.
Degradation of ALK fusion proteins in human NCI-H2228 lung cancer cells.
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36986673 |
| SU-DHL-1 | IC50 |
33 nM
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Inhibition of proliferation in human SU-DHL-1 lymphoma cells.
Inhibition of proliferation in human SU-DHL-1 lymphoma cells.
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36986673 |
体外実験
MS4078 (compound 6) binds to DNA-tagged ALK protein with high affinity, with a Kd value of 19 nM[1].
MS4078 (1-100 nM; 16 h) potently degrades the NPM-ALK fusion protein in a concentration-dependent manner, with a DC50 of 11 nM, and inhibits the downstream ALK/STAT3 signaling pathway after 16 hours of treatment in SU-DHL-1 cells[1].
MS4078 (30 nM; 2-24 h) degrades the NPM-ALK fusion protein and inhibits the downstream ALK/STAT3 signaling pathway in SU-DHL-1 cells in a time-dependent manner. At a concentration of 30 nM, its degradation effect peaks at 16 h and persists for at least 24 h[1].
MS4078 (100 nM; 6 h)-induced degradation of the NPM-ALK fusion protein in SU-DHL-1 cells is mediated by a CRBN- and proteasome-dependent mechanism[1].
MS4078 (100 nM; 2 h)-induced degradation of the NPM-ALK fusion protein and the inhibition of downstream signaling pathways in SU-DHL-1 cells are reversible, and these effects diminish 8 h after washout[1].
MS4078 (3-100 nM; 16 h) potently degrades the EML4-ALK fusion protein in a concentration-dependent manner, with a DC50 of 59 nM, and inhibits ALK autophosphorylation in NCI-H2228 cells after 16 hours of treatment[1].
MS4078 (60 nM; 2-24 h) degrades the EML4-ALK fusion protein and inhibits the downstream ALK/STAT3 signaling pathway in a time-dependent manner in NCI-H2228 cells. At a concentration of 60 nM, significant degradation is observed at 8 h, peak degradation occurs at 16 h, and the effect persists for at least 24 h[1].
MS4078 (administered for 3 consecutive days) potently inhibits the proliferation of SU-DHL-1 cells, with an IC50 of 33 nM after 3 days of treatment[1].
MS4078 binds potently to ALK (Kd = 19 nM), degrades ALK fusion proteins in SU-DHL-1 (DC50 =11 nM) and NCI-H2228 (DC50 = 59 nM) cells, and inhibits the proliferation of SU-DHL-1 cells (IC50 = 33 nM)[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SU-DHL-1 human anaplastic large-cell non-Hodgkin's lymphoma cells expressing NPM-ALK fusion protein
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Concentration:1, 3, 10, 30, 100 nM
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Incubation Time:16 h
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Result:Reduced NPM-ALK fusion protein levels in a concentration-dependent manner, achieving over 90% reduction at 100 nM.
Achieved a DC50 (50% degradation concentration) for NPM-ALK degradation of 11 nM.
Potently inhibited ALK Y1507 phosphorylation and STAT3 Y705 phosphorylation, with over 90% inhibition of both at 100 nM.
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Cell Line:SU-DHL-1 human anaplastic large-cell non-Hodgkin's lymphoma cells expressing NPM-ALK fusion protein
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Concentration:30 nM
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Incubation Time:2, 4, 8, 16, 24 h
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Result:Inhibited p-ALK and p-STAT3 significantly after 2-hour treatment.
Achieved over 50% NPM-ALK degradation by 4-hour treatment.
Observed maximum NPM-ALK degradation after 16-hour treatment, and both degradation and signaling inhibition were sustained for at least 24 hours.
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Cell Line:SU-DHL-1 human anaplastic large-cell non-Hodgkin's lymphoma cells expressing NPM-ALK fusion protein
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Concentration:100 nM
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Incubation Time:6 h
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Result:Pre-treatment with pomalidomide, MLN4924, or MG-132 significantly rescued NPM-ALK degradation induced by MS4078, confirming dependency on cereblon (CRBN), cullin RING ligase (CRL) activity, and proteasome function.
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Cell Line:SU-DHL-1 human anaplastic large-cell non-Hodgkin's lymphoma cells expressing NPM-ALK fusion protein
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Concentration:100 nM
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Incubation Time:2 h
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Result:The effects of MS4078 on NPM-ALK degradation and inhibition of ALK downstream signaling began to diminish at 8 hours after compound removal, confirming reversible degradation activity.
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Cell Line:NCI-H2228 human non-small-cell lung cancer cells expressing EML4-ALK fusion protein
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Concentration:3, 10, 30, 60, 100 nM
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Incubation Time:16 h
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Result:Reduced EML4-ALK fusion protein levels in a concentration-dependent manner, achieving over 90% reduction at 100 nM.
Achieved a DC50 for EML4-ALK degradation of 59 nM.
Potently and concentration-dependently inhibited ALK auto phosphorylation.
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Cell Line:NCI-H2228 human non-small-cell lung cancer cells expressing EML4-ALK fusion protein
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Concentration:60 nM
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Incubation Time:2, 4, 8, 16, 24 h
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Result:Observed significant EML4-ALK degradation and ALK signaling inhibition after 8-hour treatment.
Observed maximum EML4-ALK degradation after 16-hour treatment, and both degradation and signaling inhibition were sustained for at least 24 hours.
Parmacokinetics
体内実験
MS4078 (0.5-10 mg/kg; intravenous, oral; single administration) exhibits moderate in vivo clearance in female CD-1 mice when administered intravenously in a vehicle containing Kolliphor. When administered orally as a Kolliphor-containing solution and an SDD formulation, respectively, the oral bioavailability in mice is low, at 3.5% and 1.3%[2].
MS4078 (50 mg/kg; single dose), an ALK-targeting CRBN-recruiting PROTAC, exhibits favorable in vivo pharmacokinetic properties with excellent plasma exposure and tolerability in mice[3].
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 peak plasma concentration of 3000 nM at 2 hours post-dosing.
Remained at 340 nM at 12 hours post-dosing.
Was well tolerated with no observable adverse effects.
化学情報
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CAS 番号 2229036-62-6
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性状 Solid
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分子量 914.47
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分子式 C45H52ClN9O8S
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Color Light yellow to yellow
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SMILES
CC(C)S(C1=C(NC2=NC(NC3=C(OC(C)C)C=C(C4CCN(CC(NCCNC5=C(C(N(C6C(NC(CC6)=O)=O)C7=O)=O)C7=CC=C5)=O)CC4)C(C)=C3)=NC=C2Cl)C=CC=C1)(=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 2 years -20°C 1 year
Publications (4)
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Journal Impact Factor
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Most Recent
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Int J Pharm
2024 Jan 25:650:123725. PMID: 38113976 -
Colloids Surf B Biointerfaces
Precision targeting of ALK-positive lung cancer: Engineering HFN@MS4078 nanocages for optimized PROTAC delivery. [Abstract]2025 Jul 22:255:114974. PMID: 40712494 -
Mol Pharm
PROTAC Enabling Formulation In Vivo: Implications of the Polymeric Carrier Eudragit E PO. [Abstract]2025 Aug 24. PMID: 40849796 -
Structure
PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network. [Abstract]2024 Dec 5;32(12):2352-2363.e8. PMID: 39389062
溶剤 & 溶解度
体外:
DMSO : 50 mg/mL (54.68 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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: 2.08 mg/mL (2.27 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.08 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 (20.8 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.
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.
純度とドキュメンテーション
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データシート (290 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Zhang C, et al. Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK). European journal of medicinal chemistry. 2018 May 10;151:304-314. [Content Brief]
[2]. Hofmann N, et al. PROTAC Enabling Formulation : Implications of the Polymeric Carrier Eudragit E PO. Molecular pharmaceutics. 2025 Oct 06;22(10):5845-5859. [Content Brief]
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0935 mL | 5.4676 mL | 10.9353 mL | 27.3382 mL |
| 5 mM | 0.2187 mL | 1.0935 mL | 2.1871 mL | 5.4676 mL | |
| 10 mM | 0.1094 mL | 0.5468 mL | 1.0935 mL | 2.7338 mL | |
| 15 mM | 0.0729 mL | 0.3645 mL | 0.7290 mL | 1.8225 mL | |
| 20 mM | 0.0547 mL | 0.2734 mL | 0.5468 mL | 1.3669 mL | |
| 25 mM | 0.0437 mL | 0.2187 mL | 0.4374 mL | 1.0935 mL | |
| 30 mM | 0.0365 mL | 0.1823 mL | 0.3645 mL | 0.9113 mL | |
| 40 mM | 0.0273 mL | 0.1367 mL | 0.2734 mL | 0.6835 mL | |
| 50 mM | 0.0219 mL | 0.1094 mL | 0.2187 mL | 0.5468 mL |
MS4078 関連分類
HY-112155 関連分類
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Keywords
- MS4078
- 2229036-62-6
- MS 4078
- MS-4078
- PROTACs
- Anaplastic lymphoma kinase (ALK)
- STAT
- STAT3
- NPM-ALK fusion protein
- anaplastic lymphoma kinase
- human oncogenic active ALK fusion proteins
- non-small cell lung cancer
- EML4-ALK fusion protein
- cereblon
- anaplastic large-cell non-Hodgkin's lymphoma
- NCI-H2228 cells
- SU-DHL-1 cells
- Inhibitor
- inhibitor
- inhibit