VVD-214 is a synthetic lethal allosteric inhibitor of WRN helicase. VVD-214 covalently binds to cysteine 727 of WRN and inhibits ATP hydrolysis and helicase activity. VVD-214 causes cell death in microsatellite instability (MSI)-high cancers through double-strand DNA breaks and nuclear swelling.

Physicochemical Properties

Molecular Formula	C20H21F2N3O4S
Molecular Weight	437.46
Exact Mass	437.122
CAS #	3026500-20-6
PubChem CID	170717998
Appearance	Solid powder
Density	1.355±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
Boiling Point	627.5±55.0 °C(predicted)
LogP	2.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	30
Complexity	731
Defined Atom Stereocenter Count	1
SMILES	O(C1C=CC=CC=1)C1=NC(=NC=C1C(=O)N[C@@H](C1CC1)/C=C/S(=O)(=O)C)C(F)(F)C
InChi Key	UWPFUBNCDABUEE-SIFUEBAJSA-N
InChi Code	InChI=1S/C20H21F2N3O4S/c1-20(21,22)19-23-12-15(18(25-19)29-14-6-4-3-5-7-14)17(26)24-16(13-8-9-13)10-11-30(2,27)28/h3-7,10-13,16H,8-9H2,1-2H3,(H,24,26)/b11-10+/t16-/m1/s1
Chemical Name	N-[(E,1S)-1-cyclopropyl-3-methylsulfonylprop-2-enyl]-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5-carboxamide
Synonyms	RO7589831; VVD-133214
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
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

References

[1]. Abstract ND11: Chemoproteomic-enabled discovery of VVD-214, a synthetic lethal allosteric inhibitor of WRN helicase[J]. Cancer Research, 2024, 84(7_Supplement): ND11-ND11.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (228.59 mM; with sonication)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.71 mM)(Saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make it 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: ≥ 2.5 mg/mL (5.71 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, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2859 mL	11.4296 mL	22.8592 mL
	5 mM	0.4572 mL	2.2859 mL	4.5718 mL
	10 mM	0.2286 mL	1.1430 mL	2.2859 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.