Art. -Nr.: HY-112156

MS4077

Name: MS4077
Brand: MedChemExpress
SKU: HY-112156
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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 K_d 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)).

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Reinheit: 99.66%
CAS. Nr.: 2230077-10-6
Formel: C₅₅H₇₂ClN₉O₁₃S
Molecular Weight:1134.73

Speicherung:

-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)

MS4077 Chemical Structure

CAS. Nr.: 2230077-10-6

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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 K_d 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^[1]^[2]^[3]^[4]. (Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-15656); Blue: Cereblon ligand (HY-14658); Black: linker (HY-130447)).

IC₅₀ & Target

^[1]

ALK

37 nM (Kd)

ALK

3 nM (DC₅₀, SU-DHL-1 cells)

ALK

34 nM (DC₅₀, NCI-H2228 cells)

STAT3

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle STAT Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
SU-DHL-1	DC₅₀	3 nM	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.	36064579
NCI-H2228	DC₅₀	34 nM	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.	36064579
SU-DHL-1	IC₅₀	46 nM	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.	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 K_d 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.

Western Blot Analysis^[1]

Cell Line:

SU-DHL-1 human anaplastic large-cell non-Hodgkin's lymphoma cells (expressing NPM-ALK)
Concentration:

1, 3, 10, 30, 100 nM (16 h assay); 30 nM (time-course studies); 100 nM (mechanism rescue assays; washout assays)
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)
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.

Western Blot Analysis^[1]

Cell Line:

NCI-H2228 human non-small cell lung cancer cells (expressing EML4-ALK)
Concentration:

3, 10, 30, 60, 100 nM (16 h assay); 60 nM (time-course studies)
Incubation Time:

16 h (serial dilution assay); 2, 4, 8, 16, 24 h (time-course studies)
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

CAS. Nr. 2230077-10-6
Appearance Solid
Molecular Weight 1134.73
Formel C₅₅H₇₂ClN₉O₁₃S
Color Yellow to green
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

-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)

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

0.8813 mL

4.4063 mL

8.8127 mL

5 mM

0.1763 mL

0.8813 mL

1.7625 mL

10 mM

0.0881 mL

0.4406 mL

0.8813 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (281 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

[3]. Cieślak M, et al. Cereblon-Recruiting PROTACs: Will New Drugs Have to Face Old Challenges?. Pharmaceutics. 2023 Mar 02;15(3):812.

[4]. Sun X, et al. PROTACs: great opportunities for academia and industry. Signal transduction and targeted therapy. 2019;4:64. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

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MS4077

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle STAT Isoform-spezifische Produkte anzeigen