GSK2981278 is recognized as a potent and selective inverse agonist of RORγ, effectively inhibiting the activation of the IL17 promoter and disrupting RORγ-DNA binding[1].
体内研究
Topical application of GSK2981278 (1% in ointment; for three days) results in a reduction of skin redness and scaling, along with a 23% reduction in epidermal thickness, indicating its effectiveness in attenuating inflammation in a mouse model of psoriasis[1].
体外研究
GSK2981278 significantly suppresses IL-17A and IL-22 protein secretion in a concentration-dependent manner with an IC50 of 3.2 nM, especially noticeable during 5 days of culture under Th17 skewing conditions[1].
At varying concentrations (0.3, 1, 3, 10, 30, 100, 300, 1000 pM; over 5 days), GSK2981278 shows potent and selective inhibition of IL-17 and IL-22 levels, with concentrations ≥3 nM leading to nearly complete inhibition of IL-17A protein secretion[1].
GSK2981278 细胞实验
Cell Line
Concentration
Treated Time
Description
References
bursal B lymphocyte
1 μM
30 min
As a RORγ antagonist, GSK2981278 mimicked the inhibitory effect of melatonin on B-lymphocyte apoptosis, decreased IL-6, TNF-α, IFN-γ and ROS production, down-regulated p-iκb and p-p65 protein expression, whereas it improved the IL-10 level and Nrf2 and HO-1 protein expression.
Antioxidants (Basel). 2022 Apr 8;11(4):748.
bursal B lymphocytes
1 μM
30 min
GSK2981278, as a RORγ antagonist, co-treated with LPS and melatonin, significantly reduced the expression of Bax and Caspase-3 proteins, increased the expression of Bcl-2 protein, and inhibited the apoptosis of B lymphocytes.
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