MS4077
Based on 1 Customer Validation
MS4077 is an ALK PROTAC degrader with a DC50 of 3 nM in SU-DHL-1 cells, a DC50 of 34 nM in NCI-H2228 cells, and a Kd of 37 nM. MS4077 induces the degradation of oncogenic active ALK fusion proteins via a cereblon- and proteasome-dependent pathway, and inhibits the phosphorylation of ALK and STAT3, thereby suppressing cancer cell proliferation. MS4077 is used for the research of anaplastic large cell lymphoma and non-small cell lung cancer.
(Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-15656); Blue: Cereblon ligand (HY-14658); Black: linker (HY-130447)).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 99.66%
- CAS No.: 2230077-10-6
- Formule: C55H72ClN9O13S
- Masse moléculaire:1134.73
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Stockage:
-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)
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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
ALK 37 nM (Kd) |
ALK 3 nM (DC50, SU-DHL-1 cells) |
ALK 34 nM (DC50, NCI-H2228 cells) |
STAT3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| SU-DHL-1 | DC50 |
3 nM
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Degradation of NPM-ALK protein in human SU-DHL-1 cells after 16 hours treatment, analyzed via western blot.
Degradation of NPM-ALK protein in human SU-DHL-1 cells after 16 hours treatment, analyzed via western blot.
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36064579 |
| NCI-H2228 | DC50 |
34 nM
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Degradation of EML4-ALK protein in human NCI-H2228 cells after 16 hours treatment, analyzed via western blot.
Degradation of EML4-ALK protein in human NCI-H2228 cells after 16 hours treatment, analyzed via western blot.
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36064579 |
| SU-DHL-1 | IC50 |
46 nM
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Antiproliferative activity against human SU-DHL-1 cells assessed as reduction in cell viability incubated for 3 days by CellTiter-Glo luminescent assay.
Antiproliferative activity against human SU-DHL-1 cells assessed as reduction in cell viability incubated for 3 days by CellTiter-Glo luminescent assay.
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36064579 |
In Vitro
MS4077 degrades NPM-ALK and EML4-ALK, inhibits the phosphorylation of ALK and STAT3 in a concentration- and time-dependent manner, and exhibits potent antiproliferative activity in SU-DHL-1 ALCL cells[4].
MS4077 (1-100 nM; 2-24 h) degrades the NPM-ALK protein in SU-DHL-1 cells in a concentration- and time-dependent manner, with a DC50 of 3 nM. It inhibits the phosphorylation of downstream ALK and STAT3 via cereblon-dependent and proteasome-dependent mechanisms, and these effects are reversible after washout of the compound[1].
MS4077 (3-100 nM; 2-24 h) degrades the EML4-ALK protein in NCI-H2228 cells in a concentration- and time-dependent manner, with a DC50 of 34 nM, and inhibits the downstream phosphorylation of ALK[1].
MS4077 (3 days) potently inhibits the proliferation of SU-DHL-1 cells, with an IC50 of 46 nM[1].
MS4077 (compound 5) binds to purified ALK protein with high affinity, with a Kd value of 37 nM[1].
MS4077 potently downregulates the protein levels of ALK and PFKFB3 in the anaplastic large cell lymphoma cell line SU-DHL-1[2].
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)
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Concentration:1, 3, 10, 30, 100 nM (16 h assay); 30 nM (time-course studies); 100 nM (mechanism rescue assays; washout assays)
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Incubation Time:16 h (serial dilution assay); 2, 4, 8, 16, 24 h (time-course studies); 6 h (mechanism rescue assays); 2 h (washout assays)
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Result:Reduced NPM-ALK protein levels in a concentration-dependent manner, with a DC50 = 3 nM after 16 hours; over 90% reduction was achieved at 100 nM.
Inhibited ALK Y1507 phosphorylation and STAT3 Y705 phosphorylation by over 90% at 100 nM.
Significantly inhibited ALK and STAT3 phosphorylation after 2 hours, while > 50% NPM-ALK degradation was observed after 4 hours, with maximum degradation at 16 hours; effects sustained for at least 24 hours.
Rescued degradation by pre-treatment with pomalidomide, MLN4924, or MG-132, confirming cereblon and proteasome dependence.
Showed degradation and signaling inhibition began to diminish 8 hours after compound removal.
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Cell Line:NCI-H2228 human non-small cell lung cancer cells (expressing EML4-ALK)
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Concentration:3, 10, 30, 60, 100 nM (16 h assay); 60 nM (time-course studies)
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Incubation Time:16 h (serial dilution assay); 2, 4, 8, 16, 24 h (time-course studies)
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Result:Reduced EML4-ALK protein levels in a concentration-dependent manner, with a DC50 = 34 nM after 16 hours; over 90% reduction was achieved at 100 nM.
Inhibited ALK Y1507 phosphorylation in a concentration-dependent manner.
Observed significant EML4-ALK degradation and signaling inhibition after 8 hours, with maximum degradation at 16 hours; effects sustained for at least 24 hours.
Chemical Information
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CAS No. 2230077-10-6
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Appearance Solid
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Masse moléculaire 1134.73
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Formule C55H72ClN9O13S
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Color Yellow to green
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SMILES
CC(C)S(C1=C(NC2=NC(NC3=C(OC(C)C)C=C(C4CCN(CC(NCCOCCOCCOCCOCCOCCNC5=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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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
-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)
Solvant et solubilité
In Vitro:
DMSO : 110 mg/mL (96.94 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
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: 6 mg/mL (5.29 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 6 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 (60.0 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 6 mg/mL (5.29 mM); Clear solution
This protocol yields a clear solution of ≥ 6 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (60.0 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 (sealed storage, away from moisture and light)
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.
Pureté et documentation
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Fiche technique (281 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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Instruction de manipulation (2659 KB)
Références
[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]. Hu M, et al. ALK fusion promotes metabolic reprogramming of cancer cells by transcriptionally upregulating PFKFB3. Oncogene. 2022 Sep;41(40):4547-4559. [Content Brief]
[4]. Sun X, et al. PROTACs: great opportunities for academia and industry. Signal transduction and targeted therapy. 2019;4:64. [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, 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 | 0.8813 mL | 4.4063 mL | 8.8127 mL | 22.0317 mL |
| 5 mM | 0.1763 mL | 0.8813 mL | 1.7625 mL | 4.4063 mL | |
| 10 mM | 0.0881 mL | 0.4406 mL | 0.8813 mL | 2.2032 mL | |
| 15 mM | 0.0588 mL | 0.2938 mL | 0.5875 mL | 1.4688 mL | |
| 20 mM | 0.0441 mL | 0.2203 mL | 0.4406 mL | 1.1016 mL | |
| 25 mM | 0.0353 mL | 0.1763 mL | 0.3525 mL | 0.8813 mL | |
| 30 mM | 0.0294 mL | 0.1469 mL | 0.2938 mL | 0.7344 mL | |
| 40 mM | 0.0220 mL | 0.1102 mL | 0.2203 mL | 0.5508 mL | |
| 50 mM | 0.0176 mL | 0.0881 mL | 0.1763 mL | 0.4406 mL | |
| 60 mM | 0.0147 mL | 0.0734 mL | 0.1469 mL | 0.3672 mL | |
| 80 mM | 0.0110 mL | 0.0551 mL | 0.1102 mL | 0.2754 mL |
MS4077 Related Classifications
HY-112156 Related Classifications
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