GW806742X hydrochloride

GW806742X hydrochloride, 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 hydrochloride has activity against VEGFR2 (IC50=2 nM). GW806742X hydrochloride retards MLKL membrane translocation and inhibits necroptosis.

Product information

Molecular Weight: 610.01

Formula: C25H23ClF3N7O4S

Chemical Name: 3-{4-[methyl({2-[(3-sulfamoylphenyl)amino]pyrimidin-4-yl})amino]phenyl}-1-[4-(trifluoromethoxy)phenyl]urea hydrochloride

Smiles: Cl.CN(C1C=CC(=CC=1)NC(=O)NC1C=CC(=CC=1)OC(F)(F)F)C1=CC=NC(NC2C=CC=C(C=2)S(N)(=O)=O)=N1

InChiKey: RXKWLRYRNSVTJY-UHFFFAOYSA-N

InChi: InChI=1S/C25H22F3N7O4S.ClH/c1-35(22-13-14-30-23(34-22)31-18-3-2-4-21(15-18)40(29,37)38)19-9-5-16(6-10-19)32-24(36)33-17-7-11-20(12-8-17)39-25(26,27)28;/h2-15H,1H3,(H2,29,37,38)(H,30,31,34)(H2,32,33,36);1H

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

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;111(42):15072-15077.
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.

Products are for research use only. Not for human use.