GW806742X HCl is an ATP mimetic and a potent MLKL inhibitor that binds to the MLKL pseudokinase domain with a Kd of 9.3 μM. GW806742X HCl has anti-VEGFR2 activity (IC50=2 nM). GW806742X HCl delays MLKL membrane translocation and inhibits necrosis.

Physicochemical Properties

Molecular Formula	C25H23CLF3N7O4S
Molecular Weight	610.01
Related CAS #	GW806742X;579515-63-2
Appearance	White to off-white solid powder
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: Please store this product in a sealed and protected environment, 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	MLKL 9.3 μM (Kd) VEGFR2 2 nM (IC50)
ln Vitro	In a dose-dependent manner, GW806742X (0.1-10000 nM) prevents the necroptotic mortality of wild-type mouse dermal fibroblasts (MDFs) treated with TSQ (1 ng/mL TNF, 500 nM compound A (Smac mimic), and 10 μM Q-VD-OPh)[1]. GW806742X exhibits an IC50 of 5 nM for VEGF-induced suppression of HUVEC proliferation[2].
References	[1]. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci U S A. 2014;111(42):15072-15077. [2]. Discovery of a novel and potent series of dianilinopyrimidineurea and urea isostere inhibitors of VEGFR2 tyrosine kinase. Bioorg Med Chem Lett. 2005;15(15):3519-3523.

Solubility Data

Solubility (In Vitro)

DMSO :~100 mg/mL (~163.93 mM) H2O :< 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.10 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 25.0 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	1.6393 mL	8.1966 mL	16.3932 mL
	5 mM	0.3279 mL	1.6393 mL	3.2786 mL
	10 mM	0.1639 mL	0.8197 mL	1.6393 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.