RORγt Inverse agonist 10

RORγt Inverse agonist 10 is a potent and orally bioavailable RORγt (retinoic acid receptor-related orphan nuclear receptor gamma t) inverse agonist, with an IC50 of 51 nM. RORγt is a major transcription factor of genes related to psoriasis pathogenesis such as IL-17A, IL-22, and IL-23R[1]

Signaling Pathways >> Metabolic Enzyme/Protease >> ROR

Research Areas >> Inflammation/Immunology

RORγt:51 nM (IC50)

RORγt Inverse agonist 10 has a good liver microsome stability (human CLint=0.010 mL/min/mg, mouse CLint=0.030 mL/min/mg)[1]. RORγt Inverse agonist 10 suppresses the IL-17A production in a dose-dependent manner with an IC50 of 130 nM in a human whole-blood assay[1].

RORγt Inverse agonist 10 (3-100 mg/kg; p.o.) shows robust and dose-dependent inhibitory effect on the IL-17A production in mouse IL-18/23-induced cytokine expression model[1]. RORγt Inverse agonist 10 (1.145 mg/kg; p.o.) shows a high AUC of 15000 nM*h and t1/2 of 3.6 hours[1]. Animal Model: C57/BL6 male mice, mouse IL-18/23-induced cytokine expression model[1] Dosage: 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg Administration: Oral administration Result: Significantly inhibited the IL-17A production in a dose-dependent manner. Animal Model: Mice[1] Dosage: 1.145 mg/kg (Pharmacokinetic Analysis) Administration: Oral administration Result: AUC=15000 nM*h, t1/2=3.6 hours.

[1]. Ryota Nakajima, et al. Discovery of [1,2,4]Triazolo[1,5- a]pyridine Derivatives as Potent and Orally Bioavailable RORγt Inverse Agonists. ACS Med Chem Lett. 2020 Feb 27;11(4):528-534.