GW806742X is a novel and potent inhibitor of Mixed Lineage Kinase Domain-Like protein (MLKL) which binds the MLKL pseudokinase domain with a Kd value of 9.3 μM and has anti-necroptosis activity. GW806742X has activity against VEGFR2.
Physicochemical Properties
| Molecular Formula | C25H22F3N7O4S |
| Molecular Weight | 573.5469 |
| Exact Mass | 573.14 |
| Elemental Analysis | C, 52.35; H, 3.87; F, 9.94; N, 17.10; O, 11.16; S, 5.59 |
| CAS # | 579515-63-2 |
| Related CAS # | GW806742X hydrochloride |
| PubChem CID | 5329829 |
| Appearance | White to off-white solid powder |
| Density | 1.5±0.1 g/cm3 |
| Index of Refraction | 1.666 |
| LogP | 3.13 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 40 |
| Complexity | 922 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1=C([H])C([H])=C([H])C(=C1[H])N([H])C1=NC([H])=C([H])C(=N1)N(C([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1[H])N([H])C(N([H])C1C([H])=C([H])C(=C([H])C=1[H])OC(F)(F)F)=O)(N([H])[H])(=O)=O |
| InChi Key | SNRUTMWCDZHKKM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H22F3N7O4S/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) |
| Chemical Name | 1-[4-[methyl-[2-(3-sulfamoylanilino)pyrimidin-4-yl]amino]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea |
| Synonyms | GW806742-X; GW806742 X; GW806742X |
| 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
| Targets | MLKL (Kd = 9.3 μM); VEGFR2 (IC50 = 2 nM) |
| ln Vitro |
GW806742X (0.1-10000 nM) inhibits dose-dependently the necroptotic death of TSQ-stimulated wild-type mouse dermal fibroblasts (MDFs) (1 ng/mL TNF, 500 nM compound A (Smac mimetic), 10 μM Q-VD-OPh)[1]. GW806742X shows inhibition of VEGF induced proliferation of HUVECs with an IC50 of 5 nM[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 Oct 21;111(42):15072-7. [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 (~174.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 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: ≥ 2.08 mg/mL (3.63 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 20.8 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 3: ≥ 2.08 mg/mL (3.63 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 20.8 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 | 1.7435 mL | 8.7176 mL | 17.4353 mL | |
| 5 mM | 0.3487 mL | 1.7435 mL | 3.4871 mL | |
| 10 mM | 0.1744 mL | 0.8718 mL | 1.7435 mL |