GSK-2982772

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK-2982772 是一种有效的、选择性的 ATP 竞争性 RIP1 激酶抑制剂，IC50 为 16 nM。

GSK-2982772 is a potent, selective, ATP competitive RIP1 kinase inhibitor with IC50 of 16 nM; inhibits RIP1-dependent inflammatory cytokine MIP-1β production in human whole blood with IC50 of 0.5 nM, reduces spontaneous production of cytokines (IL-1β and IL-6) in a concentration-dependent fashion from ulcerative colitis explant tissue; shows potential for the treatment of inflammatory diseases in vivo.Psoriasis Phase 2 Clinical(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).

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.

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).

GSK2982772

Apoptosis

RIP kinase

RIP kinase

Inflammation/Immunology

Psoriasis

1622848-92-3

377.404

C20H19N5O3

>98% (HPLC)

DMSO : ≥ 100 mg/mL 264.97 mM

CN1C2=CC=CC=C2OCC(C1=O)NC(=O)C3=NNC(=N3)CC4=CC=CC=C4

(S)-3-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-1H-1,2,4-triazole-5-carboxamide

(-20℃)

With Ice Pack

≥ 2 years