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| 25mg |
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| 100mg |
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Purity: ≥98%
GSK'481 is a novel, potent and selective inhibitor of RIP1 (receptor interacting protein 1) WT S166 phosphorylation in human vs mouse plasmids overexpressed in HEK293T cells. Receptor Interacting Protein 1 (RIP1) Kinase has emerged as a very promising target for the treatment of numerous inflammatory diseases as a result of the recent discovery of its function in tumor necrosis factor (TNF)-mediated inflammation. This benzoxazepinone template's favorable developability profile, as demonstrated by compound GSK'481, makes it a great place to start for further optimization into a RIP1 clinical candidate.
| Targets |
RIP1 (IC50 = 1.3 nM)
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|---|---|
| ln Vitro |
The fact that GSK481 (300 nM; 2 hours; Jurkat cells) reverses the RIP3 up-regulation induced by both TNFa and shikonin in both live and dead cells suggests that necroptosis is in fact induced by both substances[2].
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| ln Vivo |
Three mouse RIP1 mutants exhibit more potent GSK481 inhibition of Ser166 phosphorylation than wild-type mice (IC50 = 18–110 nM)[1].
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| References |
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| Molecular Formula |
C21H19N3O4
|
|---|---|
| Molecular Weight |
377.393265008926
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| Exact Mass |
377.137
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| Elemental Analysis |
C, 66.83; H, 5.07; N, 11.13; O, 16.96
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| CAS # |
1622849-58-4
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| Related CAS # |
1622849-58-4
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| PubChem CID |
90351311
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| Appearance |
Light brown to brown solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
677.0±55.0 °C at 760 mmHg
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| Flash Point |
363.2±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.653
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| LogP |
2.06
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
566
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1C(CC2=CC=CC=C2)=CC(C(N[C@@H]2C(=O)N(C)C3=CC=CC=C3OC2)=O)=N1
|
| InChi Key |
KNOUWGGQMADIBV-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C21H19N3O4/c1-24-18-9-5-6-10-19(18)27-13-17(21(24)26)22-20(25)16-12-15(28-23-16)11-14-7-3-2-4-8-14/h2-10,12,17H,11,13H2,1H3,(H,22,25)/t17-/m0/s1
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| Chemical Name |
5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2-oxazole-3-carboxamide
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| Synonyms |
GSK481; GSK 481; GSK-481
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 35~75 mg/mL (92.7~198.7 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 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 25.0 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: 2.5 mg/mL (6.62 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6498 mL | 13.2489 mL | 26.4978 mL | |
| 5 mM | 0.5300 mL | 2.6498 mL | 5.2996 mL | |
| 10 mM | 0.2650 mL | 1.3249 mL | 2.6498 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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