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 (IC
50)
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
