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Overview
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Background
SR1078 is an agonist of retinoic acid receptor-related orphan receptor (ROR) RORα and RORγ with IC50 values of both 1-3 µM [1].
RORα and RORγ are two members of nuclear receptor superfamily, which possesses a highly conserved DNA-binding and a ligand-binding domain. These two receptors are considered to play important roles in the regulation of metabolism and the function of immune system [1].
SR1078 is a selective RORα and RORγ agonist, which activate RORα and RORγ directed transcription via inducing conformational changes [1].
SR1078 selectively targets on RORα and RORγ as an agonist but not on LXR and FXR [1]. It was shown that SR1078 was able to stimulate ROR activity and subsequent ROR-directed mRNA expression. When HepG2 cells were treated with SR1078 for 24h, the ROR directed reporter gene FG21 mRNA level was increased by 3-fold, while another reporter gene G6Pase was increased by 2-fold [1].
In mouse model, i.p. injection of 10 mg/kg SR1078 for 1 hr resulted in 3.6 μM plasma concentration., and after 8 hr the concentration still sustained at 800 nM. i.p. injection of 10 mg/kg SR1078 for 2 hr resulted in significantly increased level of mRNA of reporter gene G6Pase and FG21 [1].
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