RORγ
RORγ (retinoic acid receptor-related orphan receptor gamma) is a member of the nuclear receptor superfamily that functions as a DNA-binding transcription factor and regulates immune development, cellular differentiation, and tissue-specific gene expression programs[1]. The immune-associated isoform RORγt, encoded from the RORC locus through alternative promoter usage, serves as a master transcription factor that drives the differentiation of T helper 17 (Th17) cells and directly promotes expression of IL-17A and IL-17F, thereby establishing the transcriptional program of type 17 immunity[2][3]. Mechanistically, RORγt integrates cytokine-derived signals, including pathways activated by IL-6, TGF-β, and STAT3, to sustain Th17 lineage commitment and inflammatory cytokine production[3][4]. Consequently, RORγt-dependent Th17 responses contribute to the pathogenesis of multiple autoimmune and inflammatory disorders, and genetic or functional disruption of RORγt reduces Th17-cell accumulation and attenuates disease severity in experimental autoimmune models[2][4][5]. Compared with related family members such as RORα, RORγt exhibits a distinct and nonredundant role in type 17 immune programming, although cooperative activity between RORγt and RORα can further enhance Th17 differentiation in specific experimental settings[4]. Beyond immune regulation, the longer RORγ isoform displays broader tissue expression and has been associated with regulation of circadian and metabolic gene networks, distinguishing it from the lymphocyte-focused functions of RORγt[6]. For experimental applications, selective RORγt inverse agonists and antagonists suppress Th17 cytokine production while showing selectivity over related nuclear receptors, supporting their use as pharmacological tools and potential therapeutic strategies targeting the IL-23/IL-17 axis[5][7][8].
References:
- [1]. Crunkhorn S. Neurodegenerative disorders: Linking apolipoprotein E to LOAD. Nat Rev Drug Discov. 2013 Sep;12(9):664. doi: 10.1038/nrd4106. Epub 2013 Aug 19. PMID: 23954898. et al. Neurodegenerative disorders: Linking apolipoprotein E to LOAD. Nat Rev Drug Discov. 2013 Sep;12(9):664. [Content Brief]
- [2]. Ivanov II, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006 Sep 22;126(6):1121-33. [Content Brief]
- [3]. Ting AT, et al. More to Life than NF-κB in TNFR1 Signaling. Trends Immunol. 2016 Aug;37(8):535-545. [Content Brief]
- [4]. Xuexian O. Yang, et al. T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγ. Immunity 28, 29-39, January 2008. [Content Brief]
- [5]. Xue X, et al. Preclinical and clinical characterization of the RORγt inhibitor JNJ-61803534. Sci Rep. 2021 May 26;11(1):11066. [Content Brief]
- [6]. Karaś K, et al. Digoxin, an Overlooked Agonist of RORγ/RORγT. Front Pharmacol. 2019 Jan 7;9:1460. [Content Brief]
- [7]. Huh JR, et al. Small molecule inhibitors of RORγt: targeting Th17 cells and other applications. Eur J Immunol. 2012 Sep;42(9):2232-7. [Content Brief]
- [8]. Huang W, et al. Identification of Potent and Selective RORγ Antagonists. 2010 Dec 15. [Content Brief]
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RORγ Related Products (45)
Related Products (45)
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BMS-986251
0 ImagesCat. No.: HY-136527CAS No.: 2460133-35-9BMS-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).
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W6134
0 ImagesW6134 is highly potent and selective RORγ covalent inhibitor with an IC50 of 0.21 μM. W6134 exhibits excellent selectivity for RORγ over RORα, RXRγ, and ERRγ. W6134 significantly inhibits RORγ transcriptional activity W6134 inhibits the proliferation and colony formation and induces apoptosis in castration-resistant prostate cancer cells (CRPC). W6134 can be used for the research of castration-resistant prostate cancers (CRPC).
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A-9758
0 ImagesCat. No.: HY-126252CAS No.: 2055271-22-0A-9758 is a RORγ ligand and a potent, selective RORγt inverse agonist (IC50=5 nM), and exhibits robust potency against IL-17A release. A-9758 is effective in suppressing both Th17 differentiation and Th17 effector function. A-9758 significantly attenuates IL-23 driven psoriasiform dermatitis and is effective in blocking skin and joint inflammation.
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SHR168442
0 ImagesCat. No.: HY-115879CAS No.: 2382961-86-4SHR168442 is a modulator of retinoid-related orphan receptor gamma (RORγ) with an IC50 value of 0.035 μM.
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RORγt inverse agonist 35
0 ImagesCat. No.: HY-176273RORγt inverse agonist 35 (Compound 22) is a RORγt inverse agonist with an IC50 of 1.51 μM. RORγt inverse agonist 35 significantly inhibits Th17 differentiation and proinflammatory properties in human CD4+ T cells. RORγt inverse agonist 35 can be used for research of Th17-driven autoimmune diseases, such as psoriasis, multiple sclerosis, and inflammatory bowel disease (IBD).
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RORγt modulator 5
0 ImagesCat. No.: HY-142940CAS No.: 2119042-65-6RORγt 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).
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RORγt modulator 4
0 ImagesCat. No.: HY-142939CAS No.: 2188177-73-1RORγt 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).
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RORγt inhibitor 4
0 ImagesCat. No.: HY-19510CAS No.: 1426803-07-7RORγt inhibitor 4 (Compound 9a) is an orally active and a CNS-penetrating RORγt inhibitor. RORγt inhibitor 4 improves experimental autoimmune encephalomyelitis.
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RORγt inverse agonist 33
0 ImagesCat. No.: HY-169952RORγt inverse agonist 33 (compound (R)-D4) is an orally bioavailable and inverse agonists of RORγt, with the IC50 of 21 nM. RORγt inverse agonist 33 plays an important role in rheumatoid arthritis research.
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XY039
0 ImagesCat. No.: HY-163611CAS No.: 2118967-75-0
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RORγ agonist 2
0 ImagesCat. No.: HY-175361RORγ agonist 2 (Compound 34) is a selective RORγ agonist with an EC50 of 0.03 μM for hRORγ. RORγ agonist 2 significantly inhibits tumors growth in syngeneic MC38 tumor mice model.
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RORγt inverse agonist 34
0 ImagesCat. No.: HY-170370CAS No.: 2247604-77-7RORγt inverse agonist 34 (compound 5a) is a RORγt inverse agonist with an IC50 of 0.094 μM for RORγt-LBD. RORγt inverse agonist 34 is used for psoriasis research.
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RORγt inverse agonist 32
0 ImagesCat. No.: HY-168179CAS No.: 2301159-96-4RORγt inverse agonist 32 (compound b14) is orally active. RORγt inverse agonist 32 can be used in inflammation research.
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RORγt inverse agonist 29
0 ImagesCat. No.: HY-143271RORγt inverse agonist 29 is a potent, orally active and selective RORγt inverse agonist (IC50: 21 nM). RORγt inverse agonist 29 can be used in the research of skin inflammation and autoimmune diseases like psoriasis.
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CD12681
0 ImagesCat. No.: HY-111366CAS No.: 1952239-59-6
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RORγ-IN-2
0 ImagesCat. No.: HY-W545294CAS No.: 2088333-58-6RORγ-IN-2 (Compound 22) is a RORγ inhibitor, with a Ki of 16.6 nM for hRORγ. RORγ-IN-2 can be used for the research of IL-17-dependent autoimmune diseases.
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RORγt inverse agonist 36
0 ImagesCat. No.: HY-177712CAS No.: 1599530-54-7RORγt inverse agonist 36 (S configuration of Compound 16) is a RORγt inverse agonist. RORγt inverse agonist 36 can be used for the research of inflammation and immunology.
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RORγ-IN-4
0 ImagesCat. No.: HY-183145CAS No.: 1608139-41-8RORγ-IN-4 is a RORγ inhibitor with an EC50 of 0.014 μM. RORγ-IN-4 can be used for the research of inflammation.
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RORγt inverse agonist 30
0 ImagesCat. No.: HY-147533CAS No.: 1445901-41-6RORγt 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.
