MS934 is a novel improved VHL-recruiting MEK 1/2 degrader. MS934 has antiproliferation potency that suppresses the growth of HT-29 cells with a GI50 value of 0.023 μM. MS934 may be utilized to study a variety of human cancers, such as melanoma, non-small cell lung cancer (NSCLC), colorectal cancer, primary brain tumors, and hepatocellular carcinoma.

Physicochemical Properties

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)

Biological Activity

Targets	GI50: 0.023 μM (HT-29 cells)[1]
References	[1]. Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders. J Med Chem. 2020 Dec 24;63(24):15883-15905.

Solubility Data

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.