RORγ Antagonist

XY018 is a potent ROR-γ-selective antagonist. XY018 inhibits ROR-γ constitutive activity in 293T cells with high potency (EC₅₀, 190 nM). XY018 binds to the ROR-γ hydrophobic ligand binding domain (LBD).

GNE-6468 is a highly potent and selective RORγ (RORc) inverse agonist with an EC₅₀ value of 13 nM for HEK-293 cell. GNE-6468 exhibits an EC₅₀ of 30 nM for IL-17 PBMC.

F44-A13 is an orally active and highly selective farnesoid X receptor (FXR) antagonist with an IC₅₀ value of 1.1 μM. F44-A13 can optimize cholesterol metabolism and reduce its activity by inducing CYP7A1 expression. F44-A13 reduces levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) in mouse models. F44-A13 can be used in the study of metabolic diseases associated with lipid disorders.

(±)-ML 209 (compound 4n), a diphenylpropanamide, is a retinoic acid-related orphan receptor RORγ antagonist with an IC₅₀ of 1.1 μM. (±)-ML 209 inhibits RORγt transcriptional activity with an IC₅₀ of 300 nM in HEK293t cells. (±)-ML 209 inhibits the transcriptional activity of RORγt, but not RORα in cells. (±)-ML 209 selectively inhibits murine Th17 cell differentiation without affecting the differentiation of naïve CD4⁺ T cells into other lineages, including Th1 and regulatory T cells.

SR1555 is a specific retinoic acid receptor-related orphan nuclear receptor γ (RORγ) inverse agonist with an IC₅₀ value of 1 μM. SR1555 not only inhibits TH17 cell development and function but also increases the frequency of T regulatory cells, as well as inhibits the expression of IL-17. SR1555 can be used for researching autoimmune diseases.

GNE-3500 is a selective, orally active antagonist for Retinoic Acid Receptor-Related Orphan Receptor C (RORc, also known as RORγ or NR1F3) with an EC₅₀ of 12 nM. GNE-3500 exhibits good pharmacokinetic characteristics in rats.

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

BMS-986251 is an orally active and selective RORγt inverse agonist with an EC₅₀ of 12 nM for RORγt GAL4. BMS-986251 inhibits IL-17 with an EC₅₀ of 24 nM in human whole blood assay. BMS-986251 demonstrates robust efficacy in mouse acanthosis and Imiquimod-induced (HY-B0180) models (preclinical models of psoriasis).

RORγt inverse agonist 30 (Compound 1) is a potent RORγt inverse agonist with the IC₅₀ of 46 nM. Targeting the nuclear receptor RORγt is effective in autoimmune disorders.

SR-1903 is an inverse agonist of RORγ and PPARγ (IC₅₀ of ∼100 nM and 209 nM for RORγ and PPARγ, respectively) and a LXR agonist. SR-1903 exhibits anti-inflammatory and anti-diabetic efficacy in collagen-induced arthritis and diet-induced obesity mouse models.