1622848-92-3
1622848-92-3 structure
- Name: GSK2982772
- Chemical Name: GSK2982772
- CAS Number: 1622848-92-3
- Molecular Formula: C20H19N5O3
- Molecular Weight: 377.397
- Catalog: Signaling Pathways Apoptosis RIP kinase
- Create Date: 2018-01-05 18:52:09
- Modify Date: 2024-01-10 01:05:30
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GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM.
| Name | GSK2982772 |
|---|---|
| Synonyms |
1H-1,2,4-Triazole-5-carboxamide, 3-(phenylmethyl)-N-[(3S)-2,3,4,5-tetrahydro-5-methyl-4-oxo-1,5-benzoxazepin-3-yl]-
3-Benzyl-N-[(3S)-5-methyl-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-5-carboxamide T5W3M0VO9B |
| Description | GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 16 nM (human RIP1 FP), 20 nM (monkey RIP1 FP), 2 μM (rat RIP1 FP), 2.5 μM (mouse RIP1 FP)[1] |
| In Vitro | 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[1]. |
| In Vivo | GSK2982772 is dosed orally 15 min prior to TNF and shows 68, 80, and 87% protection from temperature loss over 6 h, at doses of 3, 10, and 50 mg/kg, respectively. In the corresponding TNF/zVAD model, GSK2982772 shows 13, 63, and 93% protection from temperature loss over 3 h. GSK2982772 displays a good free fraction in blood in rats (4.2%), dogs (11%), cynomolgus monkeys (11%), and humans (7.4%). The inhibitor has a good pharmacokinetic profile across both rats and monkeys. GSK2982772 distributes into a range of tissues including the colon, liver, kidney, and heart at concentrations comparable to those of blood. However, GSK2982772 has low brain penetration in rat (4%) despite possessing good cell permeability (21×10-6 cm/s)[1]. |
| Animal Admin | Mice: A total of 7 mice per dose group are orally predosed with saline or GSK2982772 at doses of 3, 10, and 50 mg/kg 15 min before i.v. administration of mouse TNF (30 μg/ mouse). Temperature loss in the mice is measured by a rectal probe. The study is terminated after 6 h when the control group lost 7 °C[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C20H19N5O3 |
| Molecular Weight | 377.397 |
| Exact Mass | 377.148804 |
| LogP | 2.08 |
| Index of Refraction | 1.676 |
| Storage condition | -20℃ |