Art. -Nr.: HY-130602

MS432

Name: MS432
Brand: MedChemExpress
SKU: HY-130602
Price: 700.00 USD
Availability: InStock
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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)).

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Reinheit : 99.72%
CAS. Nr.: 2672512-44-4
Formel: C₅₀H₆₅F₃IN₇O₆S
Molecular Weight:1076.06

Speicherung:

-20°C, protect from light, stored under nitrogen

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

MS432 Chemical Structure

CAS. Nr.: 2672512-44-4

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Top Publications Citing

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
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll (3)
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]. (Pink: MEK1 and MEK2 Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker (HY-W014831)).

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

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Cellular Effect

Cell Line	Type	Value	Description	References
HT-29	DC₅₀	31 nM	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.	31730343
HT-29	DC₅₀	17 nM	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.	31730343
SK-MEL-28	DC₅₀	31 nM	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.	31730343
SK-MEL-28	DC₅₀	9.3 nM	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.	31730343
HT-29	GI50	130 nM	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.	31730343
SK-MEL-28	GI50	83 nM	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.	31730343

In Vitro

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.

Western Blot Analysis^[1]

View Protocol

Cell Line:

HT-29 and SK-MEL-28 cells
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)
Incubation Time:

24 h
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.

Western Blot Analysis^[1]

View Protocol

Cell Line:

HT-29 and SK-MEL-28 cells
Concentration:

0.1 μM, 0.3 μM
Incubation Time:

2, 4, 8, 10, 12, 24 h
Result:

Induced time-dependent degradation of MEK1/2, with significant protein elimination observed within 4-8 hours.

Cell Proliferation Assay^[1]

View Protocol

Cell Line:

HT-29 and SK-MEL-28 cells
Concentration:

10, 30, 100 nM
Incubation Time:

14 days
Result:

Significantly and durably inhibited the colony-forming ability of tumor cells.

Parmacokinetics

Species	Dose	Route	T_max	C_max	Plasma Concentration
Mice^[1]	50 mg/kg	i.p.	0.5 h	1400 nM	710 nM

In Vivo

Animal Model:

Male Swiss Albino mice^[1].
Dosage:

50 mg/kg (Pharmacokinetic Analysis).
Administration:

IP
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.

Chemical Information

CAS. Nr. 2672512-44-4
Appearance Solid
Molecular Weight 1076.06
Formel C₅₀H₆₅F₃IN₇O₆S
Color White to off-white
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

-20°C, protect from light, stored under nitrogen

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

Lösungsmittel & Löslichkeit

In Vitro:

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)

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

0.9293 mL

4.6466 mL

9.2932 mL

5 mM

0.1859 mL

0.9293 mL

1.8586 mL

10 mM

0.0929 mL

0.4647 mL

0.9293 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 (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.

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: ≥ 2.5 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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.32 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, 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

Protokoll

All Signal Pathway Related Molecular Biology

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.
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.
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.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (275 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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]. Wei J, et al. Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader. Journal of medicinal chemistry. 2019 Dec 12;62(23):10897-10911. [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	0.9293 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

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MS432

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle MEK Isoform-spezifische Produkte anzeigen

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