A potent, selective, CNS penetrant, orally bioavailable RORγt with pIC50 of 8.3 in FRET assays.

CD12681 (CD-12681) is a potent, selective RORγ inverse agonist with IC50 of 19 nM, displays no activity against a panel of nuclear receptors (RORα, RARγ, LXRβ, PPARγ and VDR).

GNE-3500 (GNE3500) is a potent, selective, and orally bioavailable RORγ inhibitor with IC50 of 47 nM in IL-17 promoter assays.

GNE-6468 (GNE6468) is a potent and selective RORc inverse agonist (EC50=2 nM) with >1,000-fold selectivity for RORc over PPARγ.

GSK2981278 is a highly potent and selective inverse agonist of retinoic acid receptor-related orphan receptor gamma (ROR gamma).

MRL-871 (MRL871) is a potent, selective inhibitor of RORγt via allosteric inverse agonism, inhibits coactivator binding with IC50 of 7 nM; significantly reduces the IL17a mRNA levels in EL4 murine lymphoblast cell line at 10 uM.

Nobiletin (Hexamethoxyflavone)

PF-06747711 (PF06747711) is a potent, selective, orally bioavailable RORC2 (RORγt) inverse agonist with IC50 of 4.1 nM.

RORγt inverse agonist 22 is a potent, subtype selective RORγt inverse agonist with binding IC50 of 18 nM, displays >192-fold selectivity over RORα and RORβ.

RORγt inverse agonist 32 is a potent, orally bioavailable inverse agonist of RORγt with IC50 of 9 nM in SPA binding assays.

SR1001 is a high-affinity synthetic ligand of RORα and RORγ; suppresses TH17 cell differentiation and inhibits autoimmunity.

SR2211 (SR-2211) is a potent, selective RORγ inverse agonist (Ki=105 nM, IC50=320 nM) that potently inhibits production of IL-17 in cells.

TMP778 (TMP-778) is a potent, selective RORγt inhibitor with IC50 of 7 nM in FRET assays and 63 nM in IL-17 promoter assays, with no inverse agonist activity.

VTP-43742 (VTP43742) is a highly potent, selective, oral RORγt inverse agonist for the treatment of autoimmune disorders, including multiple sclerosis and psoriasis..

A potent, selective, orally bioavailable RORγt inverse agonist with IC50 of 17 nM in TR-FRET assays

TMP780 is an inverse agonist of RORγt with an IC50 of 13 nM. RORγt is a tractable drug target for the treatment of cutaneous inflammatory disorders.

TMP920 is a highly potent and selective RORγt antagonist. TMP920 inhibits RORγt binding to the SRC1 peptide with an IC50 of 0.03 μM.

FM26 (compound 25) is a potent and allosteric retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonists with an IC50 of 264 nM. FM26 has a distinct isoxazole chemotype and effectively reduces IL-17a mRNA production in EL4 cells.

Vimirogant (VTP-43742) hydrochloride is a potent, selective, and orally active RORγt inhibitor (Ki=3.5 nM; IC50=17 nM). Vimirogant hydrochloride exhibits >1000-fold selectivity versus the RORα and RORβ isotypes. Vimirogant hydrochloride inhibits Th17 differentiation and IL-17A secretion from mouse splenocytes (IC50=57 nM) without affecting Th1, Th2, or Treg cell differentiation. Vimirogant hydrochloride has the potential for autoimmune disorders research.

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 models (preclinical models of psoriasis).

RORγt Inverse agonist 6 (compound 43) is a RORγt inverse agonist for the study of Th17-driven autoimmune diseases. RORγt Inverse agonist 6 (compound 43) suppresses IL-17A gene expression by IL-23 stimulation in vivo.

RORγt inverse agonist 13 (Compound 3i) is a potent, orally active and selective RORγt inverse agonist, with improved drug-like properties, with an IC50 of 63.8 nM.

Cedirogant (ABBV-157) is an orally active RORγt inverse agonist. Cedirogant can be used for psoriasis research.

Bevurogant is a retinoid-related orphan receptor-gamma t (RORγt) antagonist. Bevurogant can be used for the research of chronic inflammatory diseases.

RORγt inverse agonist 23 is a potent, selective, and orally available novel retinoic acid receptor-related orphan receptor γt inverse agonist.

RORγ agonist 1 is a potent and orally bioavailable RORγ agonist (EC50 = 21 nM) with antitumor activity.

SHR168442 is a modulator of retinoid-related orphan receptor gamma (RORγ) with an IC50 value of 0.035 μM.

Retezorogant is a retinoid-related orphan receptor γ (RORγ) antagonist, extracted from patent WO2016093342 A1.

RORγt/DHODH-IN-3 (compound (S)-14d) is a dual RORγt/DHODH inhibitor, with IC50s of 0.098 μM and 0.432 μM, respectively. RORγt/DHODH-IN-3 exhibits remarkable in vivo anti-inflammatory activity.

RORγt/DHODH-IN-1 (compound (R)-14d) is a potent and orally active dual RORγt/DHODH inhibitor, with IC50s of 0.083 μM and 0.172 μM, respectively. RORγt/DHODH-IN-1 exhibits remarkable in vivo anti-inflammatory activity.

RORγt/DHODH-IN-2 (compound 1) is a potent dual RORγt/DHODH inhibitor. RORγt/DHODH-IN-2 can be used for inflammatory bowel disease (IBD) research.

ARN-6039 is an orally available inverse agonist of RORγ for autoimmune demyelinating disease.

RORγt modulator 5 is a RORγt modulator with a Ki value of <100 nM. RORγt modulator 5 has the potential for inflammatory, metabolic, autoimmune and other diseases mediated by RORy study (WO2017132432A1; compound 2).

RORγt modulator 4 is a RORγt modulator. RORγt modulator 4 has an activity to modulate IL-17A production in cells derived from mouse spleen (WO2018030550A1; compound 146).

RORγt inverse agonist 26 is a potent reverse agonist of RORγt. RORγt inverse agonist 26 regulates the differentiation of Th17 cells and inhibits the production of IL-17. RORγt inverse agonist 26 has the potential for the research of inflammation and autoimmune diseases (extracted from patent WO2021228215A1, compound 1) .

RORγt inverse agonist 28 is a potent reverse agonist of RORγt. RORγt inverse agonist 28 regulates the differentiation of Th17 cells and inhibits the production of IL-17. RORγt inverse agonist 28 has the potential for the research of inflammation and autoimmune diseases (extracted from patent WO2021228215A1, compound 6) .

A-9758 (A9758) is a selective, small molecule inverse agonist of retinoid-related orphan receptor gamma t (hRORγt IC50=38 nM).A-9758 also inhibits mouse RORγ transactivation with similar activity (20 nM) and is equally active on dog and rat RORγ (25 and 64 nM, repectively).A-9758 inhibits TCR-mediated IL-17A secretion with an IC50 of 100 and 38 nM in human CD4+ T cells and in vitro differentiated mouse Th17 cells, respectively.A-9758 exhibits robust potency against IL-17A release both in vitro and in vivo, significantly attenuates IL-23 driven psoriasiform dermatitis.A-9758 exhibits efficacy in an ex vivo human whole blood assay, is efficacious in human IL-17 related diseases.

BMS-986313 is a potent, selective, orally active RORγt inverse agonist with EC50 of 3.6 nM in GAL-4 reporter assay in Jurkat cell line, and 50 nM in IL-17 human whole blood assay.BMS-986313 demonstrated robust efficacy in preclinical models of psoriasis (the IMQ-induced skin lesion model and the IL-23-induced acanthosis model).

SR1555 is a selective RORγ inverse agonist (IC50=1.5 uM) that suppresses T(H)17 cells and stimulates T regulatory cells; SR1555 is devoid of LXR, FXR, and RORα activity, displaces [3H]T0901317 from the ligand binding domain (LBD) of RORγ with IC50 of 1 uM; represses the expression of RORγ while leading to increased expression of FGF21 and adipoQ in pre-adipocyctes, inhibits activation of hormone-sensitive lipase and increased fatty acid oxidation in obese diabetic mice.

(±)-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.

Izumerogant is an inverse agonist of retinoid-related orphan receptor-gamma (RORγ). Izumerogant (compound 123) also potently inhibits IL-17A, IL-17F and IFN-γ activity with IC50s <50 nM.

BMS-336 is a potent, selective, orally active RORγt (RORC2) inverse agonist with EC50 of 39 nM in RORγt reporter assays.

ODH-08 is a novel specific small molecule ligand and agonist of RORα with KD value of 8.4 um, shows potent antifibrotic effect.

PCCR-1 is a potent, specific RORγ inhibitor with binding IC50 of 34.45 nM and 778.1 nM for human and mouse RORγ, respectively, > 300-fold selectivity over other isoforms of ROR.

W6134 (RORγ covalent inhibitor 29) is a first-in-class, potent and selective RORγ covalent inhibitor with IC50 of 0.21 uM, targets the Cys320 of RORγ.