| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
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Purity: ≥98%
GSK2982772 (GSK-2982772; GSK772) is a potent, selective, oral and ATP competitive inhibitor of RIP1 (receptor Interacting Protein 1) with the potential for the treatment of inflammatory diseases. With an IC50 of 16 nM, it blocks RIP1 kinase. It was found in a DNA-encoded library and is presently undergoing a phase 2 clinical trial for ulcerative colitis, psoriatic arthritis, and rheumatoid arthritis. RIP1 controls inflammation and necroptosis, and it may be a major factor in a number of human pathologies, including immune-mediated inflammatory diseases. GSK2982772 shows more than 1,000-fold selectivity for ERK5 over a panel of over 339 kinases at 10 μM. GSK2982772 can inhibit the production of cytokines (IL-1β and IL-6) spontaneously from ulcerative colitis explant tissue in stimulated cellular systems in a concentration-dependent manner over the course of an overnight incubation. In human embryonic kidney (HEK-293) cells, GSK2982772 exhibits a weakly activating effect on the human Pregnane X receptor (hPXR) with an EC50 of 13 μM.It also exhibits a weakly concentration-dependent inhibition of hERG with an estimated IC50 of 195 μM.
| Targets |
human RIP1 FP (IC50 = 16 nM); monkey RIP1 FP (IC50 = 20 nM); rat RIP1 FP (IC50 = 2 μM); mouse RIP1 FP (IC50 = 2.5 μM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
GSK2982772 is a potent, selective, oral and ATP competitive inhibitor of RIP1 (receptor Interacting Protein 1) with an IC50 of 16 nM.
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| Cell Assay |
GSK2982772 shows more than 1,000-fold selectivity for ERK5 over a panel of over 339 kinases at 10 μM. In stimulated cellular systems,GSK2982772 is also able to reduce spontaneous production of cytokines (IL-1β and IL-6) in a concentration-dependent fashion from ulcerative colitis explant tissue in overnight incubations. GSK2982772 produces a weak concentration dependent inhibition of hERG in human embryonic kidney (HEK-293) cells, with an estimated IC50 of 195 μM, and also shows a weak activation of the human Pregnane X receptor (hPXR) with an EC50 of 13 μM.
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| Animal Protocol |
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| References |
| Molecular Formula |
C20H19N5O3
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| Molecular Weight |
377.40
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| Exact Mass |
377.148
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| Elemental Analysis |
C, 63.65; H, 5.07; N, 18.56; O, 12.72
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| CAS # |
1622848-92-3
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| Related CAS # |
1622848-92-3;1987858-31-0 (hydrate);
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| PubChem CID |
77108121
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.676
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| LogP |
2.08
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| Hydrogen Bond Donor Count |
2
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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 |
568
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1C2=C([H])C([H])=C([H])C([H])=C2N(C([H])([H])[H])C([C@]([H])(C1([H])[H])N([H])C(C1=NN([H])C(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])=N1)=O)=O
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| InChi Key |
LYPAFUINURXJSG-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C20H19N5O3/c1-25-15-9-5-6-10-16(15)28-12-14(20(25)27)21-19(26)18-22-17(23-24-18)11-13-7-3-2-4-8-13/h2-10,14H,11-12H2,1H3,(H,21,26)(H,22,23,24)/t14-/m0/s1
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| Chemical Name |
5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 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.
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 corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.51 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.51 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6497 mL | 13.2485 mL | 26.4971 mL | |
| 5 mM | 0.5299 mL | 2.6497 mL | 5.2994 mL | |
| 10 mM | 0.2650 mL | 1.3249 mL | 2.6497 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02776033 | Completed | Drug: GSK2982772 Drug: Placebo |
Psoriasis | GlaxoSmithKline | August 30, 2016 | Phase 2 |
| NCT04316585 | Completed | Drug: Placebo Drug: GSK2982772 |
Psoriasis | GlaxoSmithKline | September 28, 2020 | Phase 1 |
| NCT03590613 | Completed | Drug: Placebo Drug: GSK2982772 |
Autoimmune Diseases | GlaxoSmithKline | July 19, 2018 | Phase 1 |
| NCT02903966 | Completed | Drug: Placebo Drug: GSK2982772 |
Colitis, Ulcerative | GlaxoSmithKline | November 15, 2016 | Phase 2 |
| NCT02302404 | Completed | Drug: Placebo solution Drug: Placebo capsule |
Inflammatory Bowel Diseases | GlaxoSmithKline | January 6, 2015 | Phase 1 |
Predicted human blood concentration–time profile of benzoxazepinone5overlaid with the human whole blood inhibition IC90and IC50concentrations.J Med Chem.2017 Feb 23;60(4):1247-1261. |
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 Inhibition of overnight IL-1β and IL-6 production in human explant samples taken from ulcerative colitis patients for benzoxazepinone5in comparison to prednisolone (predni) and the corresponding RIP1 inactiveRenantiomer45.J Med Chem.2017 Feb 23;60(4):1247-1261. |
 Evaluation of benzodiazepinone5in the TNF (top) and TNF/zVAD (bottom) induced lethal shock mouse models, measuring reduction in body temperature loss over time.J Med Chem.2017 Feb 23;60(4):1247-1261. |
 Dose–response curves for benzodiazepinone5in the TNF (top) and TNF/zVAD (bottom) mouse induced lethal shock models.J Med Chem.2017 Feb 23;60(4):1247-1261. |
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 Predicted human PD dose–effect levels of benzoxaepinone5at 6.3 and 60 mg once daily, achieving 50 and 90% RIP1 inhibition levels over 24 h, respectively.J Med Chem.2017 Feb 23;60(4):1247-1261. |
 Dose proportionality for5in rat and cynomolgus monkey following oral dosing in pharmacokinetic and toxicology studies, as measured by dose normalized AUC (DNAUC).J Med Chem.2017 Feb 23;60(4):1247-1261. |
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