Keywords

• GSK2982772
• GSK-2982772
• GSK 2982772

Quick Details

• ProName: GSK2982772
• CasNo: 1622848-92-3
• Molecular Formula: C20H19N5O3
• Appearance: off-white powder
• Application: For laboratory use only- not intended ...
• ProductionCapacity: 1 Kilogram/Month
• Purity: ≥98%
• Storage: room temperature
• Transportation: by air
• LimitNum: 10 Milligram

Superiority

Details

GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC₅₀ of 16 nM. IC50 & Target: IC50: 16 nM (human RIP1 FP), 20 nM (monkey RIP1 FP), 2 μM (rat RIP1 FP), 2.5 μM (mouse RIP1 FP). 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.  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)