| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C52H69F3IN7O6S |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
MS934 is a novel, improved VHL-recruiting MEK1/2 PROTAC degrader that also degrades CRAF. It comprises a MEK1/2-binding ligand, a VHL-recruiting ligand, and a linker, and can be used to research a variety of human cancers, including melanoma, non-small cell lung cancer (NSCLC), colorectal cancer, primary brain tumors, and hepatocellular carcinoma[1][2][3]. It is supplied as a white to off-white solid (C52H69F3IN7O6S, MW 1104.11) at 98.48% purity.
Physical & Chemical Properties
| CAS Number | 2756323-15-4 |
|---|---|
| Molecular Formula | C52H69F3IN7O6S |
| Molecular Weight | 1104.11 g/mol |
| Purity | 98.48% |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | O=C(C1=C(C(F)=C(C=C1)F)NC2=C(C=C(C=C2)I)F)NOCCCCNCCCCCCCCCCCC(N[C@@H](C(C)(C)C)C(N3[C@@H](C[C@H](C3)O)C(N[C@H](C4=CC=C(C5=C(N=CS5)C)C=C4)C)=O)=O)=O |
| Target | CRAF |
| Signaling Pathway | PROTAC; MAPK/ERK Pathway |
| Solubility | In Vitro: DMSO: ≥ 50 mg/mL (45.29 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) * "≥" means soluble, but saturation unknown. |
| Storage | -20°C, protect from light, stored under nitrogen. In solvent: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
[2]. Herrera-Montávez C, et al. MEK1/2-Targeting PROTACs Promote the Collateral Degradation of CRAF in KRAS Mutant Cells. bioRxiv, 2023: 2023.06. 15.545136.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | ≥ 50 mg/mL (45.29 mM) | use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); protect from light, stored under nitrogen; avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 1.25 mg/mL (1.13 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 1.25 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (12.5 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 2
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 1.25 mg/mL (1.13 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 1.25 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (12.5 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
MS934 (0.1 nM-10 μM, 3 days) displays antiproliferative activity in human HT-29, SK-MEL-28 and SU-DHL-1 cells, with GI50 values of 23 μM, 40 nM, and 330 nM[1]. In KRAS mutant cells, MS934 (10 nM-3.3 μM, 24 h) induces collateral degradation of CRAF through a PROTAC mechanism[2].
Western Blot Analysis[2]
| Cell Line | PANC-1 cells |
|---|---|
| Concentration | 0.01, 0.04, 0.12, 0.37, 1.1 and 3.3 μM |
| Incubation Time | 24 h |
| Result | Showed a reduction in MEK1 and MEK2 protein levels, as well as active phosphorylated MEK1/2(S218/S222). Showed a dose-dependent reduction in phosphorylated CRAF(S338) and total CRAF protein levels. |
In Vivo
In mice harboring LS513 xenografts, MS934 (50 mg/kg, i.p., 2 weeks) combined with Lapatinib lowers tumor growth, with minimal effect on body weight[3].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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