GSK2982772

Cas No.:	1622848-92-3
Chemical Name:	GSK2982772,GSK-2982772,GSK 2982772
Synonyms:	GSK2982772,GSK-2982772,GSK 2982772
SMILES:	O=C(C1=NC(CC2=CC=CC=C2)=NN1)N[C@H]3COC4=CC=CC=C4N(C)C3=O
Formula:	C20H19N5O3
M.Wt:	377.4
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM.
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].
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].