GW806742X

Product NameGW806742X
CAS579515-63-2
MFC25H22F3N7O4S
MW573.55
EINECS
MOL File579515-63-2.mol

Chemical Properties

Density	1.524±0.06 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO:100.0(Max Conc. mg/mL);174.35(Max Conc. mM)
form	Solid
pka	10.09±0.60(Predicted)
color	White to off-white
InChIKey	SNRUTMWCDZHKKM-UHFFFAOYSA-N
SMILES	CN(C1=NC(NC2=CC(S(=O)(N)=O)=CC=C2)=NC=C1)C3=CC=C(NC(NC4=CC=C(OC(F)(F)F)C=C4)=O)C=C3

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Uses

GW806742X, an ATP mimetic and a potent MLKL (Mixed Lineage Kinase Domain-Like protein) inhibitor, binds the MLKL pseudokinase domain with a Kd of 9.3 μM. GW806742X has activity against VEGFR2 (IC50=2 nM). GW806742X retards MLKL membrane translocation and inhibits necroptosis[1][2].

Biological Activity

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

in vitro

GW806742X (0.1-10000 nM) inhibits necroptotic death of wild-type mouse dermal fibroblasts (MDFs) stimulated with TSQ (1 ng/mL TNF, 500 nM compound A (Smac mimetic), 10 μM Q-VD -OPh) in a dose-dependent manner. GW806742X shows inhibition of VEGF induced proliferation of HUVECs with an IC50 of 5 nM.

target

MLKL

9.3 μM (Kd)

VEGFR2

2 nM (IC _{50 < /sub> )}

IC 50

MLKL: 9.3 μM (Kd); VEGFR2: 2 nM (IC₅₀)

References

[1] Hildebrand JM, et al. 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 Oct 21;111(42):15072-7. DOI:10.1073/pnas.1408987111
[2] Sammond DM, et al. 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. DOI:10.1016/j.bmcl.2005.05.096