Art. -Nr.: HY-112155

MS4078

Name: MS4078
Brand: MedChemExpress
SKU: HY-112155
Price: 130.00 USD
Availability: InStock
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4 Cited Publications

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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 K_d 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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Reinheit: 99.72%
CAS. Nr.: 2229036-62-6
Formel: C₄₅H₅₂ClN₉O₈S
Molecular Weight:914.47

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

MS4078 Chemical Structure

CAS. Nr.: 2229036-62-6

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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
- Parmacokinetics
- In Vivo
Chemical Information
Publications (4)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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

IC₅₀ & Target

^[3]^[1]

ALK

11 nM (DC₅₀, SU-DHL-1 cells)

ALK

59 nM (DC₅₀, NCI-H2228 cells)

ALK

19 nM (Kd)

p-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	11 nM	Degradation of ALK fusion proteins in human SU-DHL-1 lymphoma cells. Degradation of ALK fusion proteins in human SU-DHL-1 lymphoma cells.	36986673
NCI-H2228	DC₅₀	59 nM	Degradation of ALK fusion proteins in human NCI-H2228 lung cancer cells. Degradation of ALK fusion proteins in human NCI-H2228 lung cancer cells.	36986673
SU-DHL-1	IC₅₀	33 nM	Inhibition of proliferation in human SU-DHL-1 lymphoma cells. Inhibition of proliferation in human SU-DHL-1 lymphoma cells.	36986673

In Vitro

MS4078 (compound 6) binds to DNA-tagged ALK protein with high affinity, with a K_d 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 (K_d = 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.

Western Blot Analysis^[1]

Cell Line:

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

1, 3, 10, 30, 100 nM
Incubation Time:

16 h
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.

Western Blot Analysis^[1]

Cell Line:

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

30 nM
Incubation Time:

2, 4, 8, 16, 24 h
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.

Western Blot Analysis^[1]

Cell Line:

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

100 nM
Incubation Time:

6 h
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.

Western Blot Analysis^[1]

Cell Line:

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

100 nM
Incubation Time:

2 h
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.

Western Blot Analysis^[1]

Cell Line:

NCI-H2228 human non-small-cell lung cancer cells expressing EML4-ALK fusion protein
Concentration:

3, 10, 30, 60, 100 nM
Incubation Time:

16 h
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.

Western Blot Analysis^[1]

Cell Line:

NCI-H2228 human non-small-cell lung cancer cells expressing EML4-ALK fusion protein
Concentration:

60 nM
Incubation Time:

2, 4, 8, 16, 24 h
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

Species	Dose	Route	C_max	T_max	AUC_last	T_1/2	CL	V_ss	F	Plasma Concentration
Mice^[2]	0.5 mg/kg	i.v.	808.3 ng/mL	0.1 h	405 ng/mL·h	1.11 h	1.22 L/h/kg	1.05 L/kg	/	/
Mice^[2]	10 mg/kg	p.o.	91.4 ng/mL	1 h	284 ng/mL·h	3.9 h	/	/	3.5 %	/
Mice^[1]	50 mg/kg	i.p.	3000 nM	/	/	/	/	/	/	340 nM

In Vivo

MS4078 (compound 6) (50 mg/kg; i.p.; single dose) achieves good plasma exposure in male Swiss albino mice following a single 50 mg/kg intraperitoneal injection, with concentrations maintained above its in vitro antiproliferative IC₅₀ for at least 12 h^[1].
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.

Animal Model:

Swiss Albino (male)^[1]
Dosage:

50 mg/kg
Administration:

i.p.; single dose
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.

Chemical Information

CAS. Nr. 2229036-62-6
Appearance Solid
Molecular Weight 914.47
Formel C₄₅H₅₂ClN₉O₈S
Color Light yellow to yellow
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

Int J Pharm

ASDs of PROTACs: Spray-dried solid dispersions as enabling formulations. [Abstract]

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

Lösungsmittel & Löslichkeit

In Vitro:

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)

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

1.0935 mL

5.4676 mL

10.9353 mL

5 mM

0.2187 mL

1.0935 mL

2.1871 mL

10 mM

0.1094 mL

0.5468 mL

1.0935 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, 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.

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 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.

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 (290 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]. 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]

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

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

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

Bioz

MS4078

4 Cited Publications

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MS4078

Publications Citing Use of MedChemExpress (MCE) MS4078

Alle PROTACs Isoform-spezifische Produkte anzeigen

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