GSK 2981278

GSK 2981278 (GSK2981278) is a potent, highly selective RORγ/RORγt inhibitor that potently inhibits IL-17A and IL-22 protein secretion in human peripheral T cell with IC50 of 3.2 nM; shows no effects on RORα-dependent activation; robustly inhibits RORγ-mediated cytokine production at both the mRNA and protein level, inhibits RORγt-mediated transactivation; attenuates inflammation in mouse model of psoriasis.Psoriasis Phase 2 Clinical (In Vitro) :GSK2981278 markedly and potently inhibits IL-17A and IL-22 protein secretion in a concentration dependent manner (IC50 = 3.2 nM) during 5 days of culture under Th17 skewing conditions.GSK2981278 (0.3, 1, 3, 10, 30, 100, 300, 1000 pM; 5 day) potently and selectively inhibits IL-17 and IL-22 levels. Culture in the presence of ≥3 nM GSK2981278 led to a near-complete inhibition of IL-17A protein secretion. (In Vivo) :GSK2981278 (1% in ointment; topically; for three days) reduces skin redness and scaling, as well as decreased hyperplasia, as evidenced by a 23% reduction in epidermal thickness. GSK2981278 attenuates inflammation in a mouse model of psoriasis.