RORγt inverse agonist 34 (compound 5a) is an inverse agonist for RORγt, exhibiting an IC50 of 0.094 μM for the inhibition of RORγt-LBD. This compound is utilized in psoriasis research.

RORγt:0.094 μM

RORγt inverse agonist 34 inhibits the recruitment of SRC1 coactivator peptide by RORγt-LBD with an IC50 of 0.094 μM [1]. It effectively suppresses Th17 cell differentiation with an IC50 of 1.57 μM [1]. The compound has a half-life of 18 minutes in mouse liver microsomes at 1 μM concentration over 1 hour [1]. Furthermore, it shows low cardiac toxicity, as indicated by an hERG inhibition IC50 exceeding 40 μM [1].

RORγt inverse agonist 34 administered at 100 mg/kg intraperitoneally daily for 7 days demonstrates significant efficacy in improving Imiquimod-induced psoriasis lesions [1]. When used as a 0.25% to 4% ointment daily for 11 days, it shows anti-psoriatic activity in a mouse model of Imiquimod-induced psoriasis [1]. In BALB/c mice, a 4% ointment applied transdermally (approximately 50 g) peaks in plasma concentration at 0.075 μg/mL after about 10 minutes [1]. Furthermore, administering a 10% to 20% mg/kg ointment daily over 12 days results in no apparent acute toxicity in BALB/c mice [1].