| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
GI50: 0.023 μM (HT-29 cells)[1]
MEK1, MEK2, CRAF |
|---|---|
| ln Vitro |
MS934 potently degrades MEK1 and MEK2 in HT29 cells with DC₅0 values of 18 nM and 9 nM, respectively. It exhibits anti‑proliferative activity against HT29 cells with a GI₅0 of 23 nM, suppresses the growth of SK‑MEL‑28, H3122, and SUDHL1 cells, degrades MEK1/2 and CRAF, and inhibits pMEK and pERK in a concentration‑dependent manner in HT‑29 and SK‑MEL‑28 cells. MS934 also degrades CRAF in cells through MEK1/2 degradation.
|
| ln Vivo |
MS934 is more potent at inhibiting the growth of HT-29, SK-MEL-28, H3122, and SUDHL1 cells. In xenograft models, MS934 suppresses tumor growth by inducing sustained MEK1/2 degradation and inhibiting downstream ERK signaling. The concurrent degradation of CRAF further enhances pathway blockade, potentially overcoming feedback activation mechanisms.
|
| Enzyme Assay |
MS934 is synthesized by linking a MEK inhibitor warhead to a VHL E3 ligase ligand. For non‑cellular binding assays, recombinant MEK1/2 proteins are incubated with MS934 (0.1‑1000 nM) in a buffer containing ATP. Binding affinity is measured by fluorescence polarization or surface plasmon resonance. Kinase activity is measured using a coupled enzymatic assay.
|
| Cell Assay |
MS934 is dissolved in DMSO and diluted to desired concentrations (final DMSO ≤0.1%). HT29, SK-MEL-28, or other cancer cells are treated with MS934 (1 nM - 10 uM) for 6‑24 h. MEK1/2 degradation is assessed by Western blotting, and pERK levels are measured. Cell proliferation is evaluated using MTT or CellTiter-Glo assays after 72 h of treatment.
|
| Animal Protocol |
MS934 is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG400, 5% Tween 80) and administered intraperitoneally or orally to mice bearing HT29 or SK-MEL-28 xenografts. Tumor tissues and plasma are collected at multiple time points for PK and PD analysis, including measurement of MEK1/2 protein levels and ERK phosphorylation.
|
| ADME/Pharmacokinetics |
No detailed PK data for MS934 has been reported. As a VHL‑recruiting PROTAC degrader, it is likely to follow the PK properties typical of PROTACs, including moderate oral bioavailability and significant first‑pass metabolism. Detailed parameters such as half‑life, Cmax, and clearance are not publicly available.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data for MS934 has been reported. As a PROTAC degrader targeting MEK1/2 and CRAF, potential off‑target degradation or proteasome saturation at high doses remains a theoretical concern. Preclinical toxicology studies would be required for advancement beyond research use.
|
| References | |
| Additional Infomation |
MS934 is a novel improved VHL‑recruiting MEK1/2 PROTAC degrader with a molecular weight of 1104.11 (C₅2H₆₉F3IN₇O₆S). It also degrades CRAF, potentially as a consequence of MEK1/2 degradation, providing a dual mechanism for MAPK pathway inhibition. MS934 can be used for research in melanoma, NSCLC, colorectal cancer, primary brain tumors, and hepatocellular carcinoma. No clinical trials or regulatory approvals have been reported.
|
| Molecular Formula |
C52H69F3IN7O6S
|
|---|---|
| Molecular Weight |
1104.11225485802
|
| Exact Mass |
1103.402
|
| CAS # |
2756323-15-4
|
| PubChem CID |
162504450
|
| Appearance |
White to off-white solid powder
|
| LogP |
11.3
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
28
|
| Heavy Atom Count |
70
|
| Complexity |
1600
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCCNCCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O
|
| InChi Key |
DYLGPTDXXUWFMK-ARFQKLFXSA-N
|
| InChi Code |
InChI=1S/C52H69F3IN7O6S/c1-33(35-18-20-36(21-19-35)47-34(2)58-32-70-47)59-50(67)43-30-38(64)31-63(43)51(68)48(52(3,4)5)61-44(65)17-13-11-9-7-6-8-10-12-14-26-57-27-15-16-28-69-62-49(66)39-23-24-40(53)45(55)46(39)60-42-25-22-37(56)29-41(42)54/h18-25,29,32-33,38,43,48,57,60,64H,6-17,26-28,30-31H2,1-5H3,(H,59,67)(H,61,65)(H,62,66)/t33-,38+,43-,48+/m0/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[12-[4-[[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]amino]oxybutylamino]dodecanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ≥ 50 mg/mL (45.29 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (1.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9057 mL | 4.5285 mL | 9.0571 mL | |
| 5 mM | 0.1811 mL | 0.9057 mL | 1.8114 mL | |
| 10 mM | 0.0906 mL | 0.4529 mL | 0.9057 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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