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RAR-related orphan receptor-γ

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Target id: 600

Nomenclature: RAR-related orphan receptor-γ

Systematic Nomenclature: NR1F3

Family: 1F. Retinoic acid-related orphans

Gene and Protein Information Click here for help
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 518 1q21 RORC RAR related orphan receptor C 12
Mouse 516 3 F2.1 Rorc RAR-related orphan receptor gamma 25
Rat - 2q34 Rorc RAR-related orphan receptor C
Gene and Protein Information Comments
Two protein isoforms, produced by alternative promoter usage, are expressed from the human RORC gene. Isoform 1 (RORC1) is the 518 amino acid full-length product. Isoform 2 (RORC2 or RORγt) is shorter, missing the first 21 amino acids of isoform 1 and having amino acids 22-24 (HTS) replaced by MRT. Isoform 2 is exclusively expressed by immature thymocytes.
Previous and Unofficial Names Click here for help
nuclear receptor ROR-gamma | nuclear receptor RZR-gamma | RORC2 | RORγ | RORγt | RZRγ | Thor | thymus orphan receptor | TOR
Database Links Click here for help
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Ligand binding domain of RORgamma in complex with endogenous ligand
PDB Id:  3L0L
Ligand:  25-hydroxycholesterol   This ligand is endogenous
Resolution:  1.74Å
Species:  Human
References:  15
Natural/Endogenous Ligands Click here for help
25-hydroxycholesterol
Comments: Orphan

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
XY101 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inverse agonist 6.1 – 6.4 pKd 35
pKd 6.4 (Kd 3.8x10-7 M) [35]
Description: In vitro binding to the RORγ LBD measured in a isothermal titration calorimetry (ITC) assay.
pKd 6.1 (Kd 7.5x10-7 M) [35]
Description: In vitro binding to the RORγ LBD measured using AlphaScreen technology.
T0901317 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inverse agonist 7.3 pKi 19
pKi 7.3 (Ki 5.1x10-8 M) [19]
SR2211 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inverse agonist 7.0 pKi 18
pKi 7.0 (Ki 1.05x10-7 M) [18]
Description: Displacement of radioligand [3H]T1317 in a competition-based SPA assay.
SR1001 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inverse agonist 6.9 pKi 30
pKi 6.9 (Ki 1.11x10-7 M) [30]
Description: Competitive radioligand binding assay using [3H]25-hydroxycholesterol as tracer.
GNE-3500 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inverse agonist 7.9 pEC50 8
pEC50 7.9 (EC50 1.2x10-8 M) [8]
Description: Measuring inhibition of SRC1 coactivator peptide recruitment by the ligand binding domain of human RORγ.
MRL-871 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inverse agonist 7.8 pEC50 7
pEC50 7.8 (EC50 1.6x10-8 M) [7]
Description: Inverse agonist activity at N-terminal 6xHis-tagged human RORc ligand binding domain (241 to 486); assessed as inhibition of SRC1 co-activator peptide recruitment after 3 hrs by TR-FRET analysis
compound 32 [PMID: 31638797] Small molecule or natural product Immunopharmacology Ligand Hs Inverse agonist 7.6 pEC50 21
pEC50 7.6 (EC50 2.4x10-8 M) [21]
Description: Determined in a luciferase reporter assay; measuring inhibition of constitutive activity of RORγt in Jurkat cells overexpressing full length RORγt proteins fused with the Gal4 Luc reporter.
cintirorgon Small molecule or natural product Immunopharmacology Ligand Hs Agonist >6.3 pEC50 1
pEC50 >6.3 (EC50 <5x10-7 M) [1]
Description: Measured in a RORγ-ligand binding domain Gal4-RORγ luciferase reporter assay.
pEC50 >6.3 (EC50 <5x10-7 M) [1]
Description: Measured in a RORγ-ligand binding domain TR-FRET assay.
compound 32 [PMID: 31638797] Small molecule or natural product Immunopharmacology Ligand Hs Inverse agonist 10.4 pIC50 4
pIC50 10.4 (IC50 3.6x10-11 M) [4]
Description: Determined in a competition binding scintillation proximity assay (SPA), using recombinant His-tagged RORγ ligand binding domain (A262-S507) and [3H] 25-hydroxycholesterol as tracer.
TAK-828F Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inverse agonist 8.7 pIC50 17
pIC50 8.7 (IC50 1.9x10-9 M) [17]
Description: Binding to human RORγt isoform.
GSK2981278 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inverse agonist 8.5 pIC50 28
pIC50 8.5 (IC50 3.2x10-9 M) [28]
Description: Measuring inhibition of human T cell cytokine production under Th17 skewing conditions.
RORC2 inverse agonist 66 [PMID: 30130103] Small molecule or natural product Immunopharmacology Ligand Hs Inverse agonist 7.8 – 8.4 pIC50 9,27
pIC50 8.4 (IC50 4.1x10-9 M) [27]
Description: In a TR-FRET assay measuring agonist-induced inhibition of co-factor recruitment to RORC2 ligand binding domain.
pIC50 7.8 (IC50 1.66x10-8 M) [9]
Description: In a TR-FRET assay measuring agonist-=induced inhibition of co-activator peptide recruitment to RORC2 ligand binding domain.
compound 14 [Schnute et al., 2023] Small molecule or natural product Immunopharmacology Ligand Hs Inverse agonist 8.0 pIC50 26
pIC50 8.0 (IC50 9.3x10-9 M) [26]
Description: Inhibitory potency in a TR-FRET cofactor recruitment assay
XY101 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inverse agonist 7.5 pIC50 35
pIC50 7.5 (IC50 3x10-8 M) [35]
Description: Measuring disruprion of RORγ-driven transcriptional activity in a Gal4 reporter assay in 293 T cells.
AZD0284 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inverse agonist 7.4 pIC50 23
pIC50 7.4 (IC50 4.1x10-8 M) [23]
SR1555 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inverse agonist 6.0 pIC50 29
pIC50 6.0 (IC50 1x10-6 M) [29]
Description: In a competitive radioligand binding assay using [3H]T0901317 as tracer and measuring displacement from the ligand binding domain fragment of RORγ.
25-hydroxycholesterol Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - - 15
[15]
Agonist Comments
Even although no ligands have been identified, hydroxycholesterols have been shown to promote the recruitment of coactivators by RORγ using biochemical assays [15].
Antagonists Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ALRT 1550 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist - - 32
[32]
Antagonist Comments
Both ALRT 1550 and all-trans retinoic acid partially inhibit RORγ transcriptional activity.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 25 [Zhang et al., 2020] Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Negative 9.0 pIC50 34
pIC50 9.0 (IC50 1x10-9 M) [34]
Description: Inhibition of cofactor (LXXLL-motif containing steroid receptor coactivator SRC1 peptide) recruitment to RORγ ligand binding domain in a TR-FRET biochemical assay.
Immunopharmacology Comments
RORγ is a nuclear receptor transcription factor that acts as an immune cell master control switch (most likely associated with expression of the RORγt isoform). This receptor is an essential regulator of type 17 effector T cell differentiation and function. RORγt inhibitors (antagonists and inverse agonists) [3,10,24,31] are in development for the treatment of autoimmune diseases such as psoriasis and rheumatoid arthritis [2,14]. Inverse agonists block RORγt-driven development and differentiation of IL-17 producing Th17 cells to reduce inflammation. Examples include AZD0284 (see the ACS webinar Psoriasis: Treatment and Novel Approaches) and GNE-3500 [8]. Development of VTP-43742 [10], Allergan's RORγ inverse agonist, was terminated in early 2018 due to safety issues detected in their Phase 2 psoriasis trial.
As immuno-oncology candidates, RORγ agonists are being studied for their potential to improve immune detection/destruction of cancer cells [13]. For example, Lycera's orally active agent cintirorgon is being evaluated in early phase clinical trial NCT02929862 in patients with locally advanced or metastatic solid tumours.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
DNA Binding Click here for help
Structure:  Homodimer
HRE core sequence:  AGGTCA nnnnn AGGTCA
Response element:  DR4, DR5, Half site
DNA Binding Comments
It has been shown that mouse RORγ does not recognise the classical ROREs but binds with high affinity as a homodimer to DR4 and DR5 elements.
Co-binding Partners Click here for help
Name Interaction Effect Reference
Mi-2beta Physical, Functional Mi-2beta: A yeast two-hybrid screen with Y190 yeast cells under stringent conditions resulted in the identification of CHD4, also known as Mi-2beta, as a RORgamma-interacting protein. This interaction was confirmed by GST pull-down assays. This interaction occurred within the middle regulatory region (amino acids 719-1164) of Mi-2beta. Transfection of Gal4-RORgamma into HeLa cells resulted in constitutive transactivation of the MH100-tk-luc reporter. The addition of Mi-2beta resulted in a dramatic 50% decrease in Gal4-RORgamma-mediated transactivation. These data demonstrate that RORgamma forms a protein-protein interaction with the regulatory region of Mi-2beta, resulting in inhibition of RORgamma transcriptional activity. 16
Main Co-regulators Click here for help
Name Activity Specific Ligand dependent AF-2 dependent Comments References
NCOA1 Co-activator No No Yes 20
HR Co-repressor No Yes Yes 22
Tissue Distribution Click here for help
Muscle, thymus, testis, pancreas, prostate, heart and liver
Expression level:  High
Species:  Human
Technique:  in situ hybridization, Immunohistology, Northern Blot, other
References:  5-6,12,25
Tissue Distribution Comments
In the human tissues RORγ was shown to be highly expressed as a 3.2 kb mRNA. In thymus, two other transcripts at 7.2 and 5.2 kb were also detected. In mouse, other authors found a predominant expression in thymus as in other tissues such as liver, heart, tongue, muscle, and diaphragm. Notably, no expression was found in spleen, or bone marrow. The major transcript is found at 2.5 kb but a 3.5 kb form is detected in several organs such as thymus. The same study reports expression in a number of mammalian cell lines. Recently, it has been shown that during fetal life, the nuclear hormone receptor RORγt is expressed exclusively in and is required for the generation of lymphoid tissue inducer cells [6,33].
Physiological Consequences of Altering Gene Expression Click here for help
ROR gamma null mice: Homozygotes for targeted null mutations exhibit lack of peripheral and mesenteric lymph nodes and Peyer's patches, reduced numbers of thymocytes, and increased apoptosis with loss of thymic expression of anti-apoptosic factor Bcl-xL
Species:  Mouse
Tissue:  Various
Technique:  Gene knockout
References:  33
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0008400 abnormal CD4-positive, alpha-beta intraepithelial T cell morphology PMID: 15247480 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0008401 abnormal CD8 positive, alpha-beta intraepithelial T cell morphology PMID: 15247480 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0000495 abnormal colon morphology PMID: 20226692 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0002378 abnormal gut-associated lymphoid tissue morphology PMID: 14691482  15247480 
Ltatm1Dch|Rorc+|Rorctm2Litt Ltatm1Dch/Ltatm1Dch,Rorctm2Litt/Rorc+
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
MGI:104797  MGI:104856  MP:0002378 abnormal gut-associated lymphoid tissue morphology PMID: 15247480 
Id2tm1Yyk|Rorc+|Rorctm2Litt Id2tm1Yyk/Id2tm1Yyk,Rorctm2Litt/Rorc+
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
MGI:104856  MGI:96397  MP:0002378 abnormal gut-associated lymphoid tissue morphology PMID: 14691482 
Id2tm1Yyk|Rorc+|Rorctm2Litt Id2tm1Yyk/Id2tm1Yyk,Rorctm2Litt/Rorc+
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
MGI:104856  MGI:96397  MP:0000716 abnormal immune system cell morphology PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0008751 abnormal interleukin level PMID: 17581589 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0002450 abnormal lymph organ development PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0002450 abnormal lymph organ development PMID: 10963675 
Id2tm1Yyk|Rorc+|Rorctm2Litt Id2tm1Yyk/Id2tm1Yyk,Rorctm2Litt/Rorc+
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
MGI:104856  MGI:96397  MP:0002450 abnormal lymph organ development PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0008826 abnormal splenic cell ratio PMID: 10963675 
Rorctm1Litt|Tcra-Jtm3Krg Rorctm1Litt/Rorctm1Litt,Tcra-Jtm3Krg/Tcra-Jtm3Krg
involves: 129P2/OlaHsd * 129S6/SvEvTac
MGI:104856  MGI:98555  MP:0002145 abnormal T cell differentiation PMID: 17882258 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0002145 abnormal T cell differentiation PMID: 17882258 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0002444 abnormal T cell physiology PMID: 10963675 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0008024 absent lymph nodes PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0008024 absent lymph nodes PMID: 10963675 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0002831 absent Peyer's patches PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0002831 absent Peyer's patches PMID: 10963675 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0002816 colitis PMID: 20226692 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0001652 colonic necrosis PMID: 20226692 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0008075 decreased CD4-positive T cell number PMID: 10963675 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0008079 decreased CD8-positive T cell number PMID: 10963675 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0005089 decreased double-negative T cell number PMID: 15247480 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0005092 decreased double-positive T cell number PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0005092 decreased double-positive T cell number PMID: 10963675 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0008045 decreased NK cell number PMID: 19084435 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0005018 decreased T cell number PMID: 10963675 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0004956 decreased thymus weight PMID: 10963675 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0000691 enlarged spleen PMID: 10963675 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0005090 increased double-negative T cell number PMID: 10963675 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0002412 increased susceptibility to bacterial infection PMID: 20226692 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0009788 increased susceptibility to bacterial infection induced morbidity/mortality PMID: 20226692 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0006413 increased T cell apoptosis PMID: 10963675 
Rorctm2Litt Rorctm2Litt/Rorctm2Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0009541 increased thymocyte apoptosis PMID: 14691482 
Rorctm1Amj Rorctm1Amj/Rorctm1Amj
either: (involves: 129/Sv * C57BL/6) or (involves: 129/Sv * C57BL/6 * DBA/2)
MGI:104856  MP:0001823 thymus hypoplasia PMID: 10963675 
Rorctm1Litt Rorctm1Litt/Rorctm1Litt
involves: 129P2/OlaHsd
MGI:104856  MP:0001263 weight loss PMID: 20226692 
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  RORγt (also known as nuclear receptor ROR-gamma isoform b or RORγ b). This variant differs in the 5' UTR and coding region compared to canonical RORγ. It is shorter and has a distinct N-terminus compared to isoform a.
Amino acids:  497
Nucleotide accession: 
Protein accession: 
References:  11

References

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1. Aicher TD, Taylor CB, Vanhuis CA. (2016) Aryl dihydro-2h-benzo[b][1,4]oxazine sulfonamide and related compounds for use as agonists of rory and the treatment of disease. Patent number: WO2016201225A1. Assignee: Lycera Corporation. Priority date: 11/06/2015. Publication date: 15/12/2016.

2. Bronner SM, Zbieg JR, Crawford JJ. (2017) RORγ antagonists and inverse agonists: a patent review. Expert Opin Ther Pat, 27 (1): 101-112. [PMID:27629281]

3. Dai J, Choo MK, Park JM, Fisher DE. (2017) Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis. J Invest Dermatol, 137 (12): 2523-2531. [PMID:28774591]

4. Duan J, Dhar TGM, Marcoux D, Shi Q, Batt DG, Liu Q, Cherney RJ, Cornelius AMC, Srivastava AS, Bertrand MB et al.. (2016) Tricyclic sulfones as rorϒ modulators. Patent number: WO2016179460A1. Assignee: Bristol-Myers Squibb. Priority date: 07/05/2015. Publication date: 10/11/2016.

5. Eberl G, Littman DR. (2003) The role of the nuclear hormone receptor RORgammat in the development of lymph nodes and Peyer's patches. Immunol Rev, 195: 81-90. [PMID:12969312]

6. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR. (2004) An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol, 5 (1): 64-73. [PMID:14691482]

7. Fauber BP, Gobbi A, Robarge K, Zhou A, Barnard A, Cao J, Deng Y, Eidenschenk C, Everett C, Ganguli A et al.. (2015) Discovery of imidazo[1,5-a]pyridines and -pyrimidines as potent and selective RORc inverse agonists. Bioorg Med Chem Lett, 25 (15): 2907-12. [PMID:26048793]

8. Fauber BP, René O, Deng Y, DeVoss J, Eidenschenk C, Everett C, Ganguli A, Gobbi A, Hawkins J, Johnson AR et al.. (2015) Discovery of 1-{4-[3-fluoro-4-((3s,6r)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a potent, selective, and orally bioavailable retinoic acid receptor-related orphan receptor C (RORc or RORγ) inverse agonist. J Med Chem, 58 (13): 5308-22. [PMID:26061388]

9. Flick AC, Jones P, Kaila N, Mente SR, Schnute ME, Trzupek JD, Vazquez ML, Xing L, Zhang L, Wennerstal GM et al.. (2016) Methyl-and trifluoromethyl-substituted pyrrolopyridine modulators of rorc2 and methods of use thereof. Patent number: WO2016046755A1. Assignee: Pfizer Inc.. Priority date: 26/09/2014. Publication date: 31/03/2016.

10. Gege C. (2016) Retinoid-related orphan receptor gamma t (RORγt) inhibitors from Vitae Pharmaceuticals (WO2015116904) and structure proposal for their Phase I candidate VTP-43742. Expert Opin Ther Pat, 26 (6): 737-44. [PMID:26895086]

11. He YW, Deftos ML, Ojala EW, Bevan MJ. (1998) RORgamma t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells. Immunity, 9 (6): 797-806. [PMID:9881970]

12. Hirose T, Smith RJ, Jetten AM. (1994) ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. Biochem Biophys Res Commun, 205 (3): 1976-83. [PMID:7811290]

13. Hu X, Liu X, Moisan J, Wang Y, Lesch CA, Spooner C, Morgan RW, Zawidzka EM, Mertz D, Bousley D et al.. (2016) Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity. Oncoimmunology, 5 (12): e1254854. [PMID:28123897]

14. Huang Z, Xie H, Wang R, Sun Z. (2007) Retinoid-related orphan receptor gamma t is a potential therapeutic target for controlling inflammatory autoimmunity. Expert Opin Ther Targets, 11 (6): 737-43. [PMID:17504012]

15. Jin L, Martynowski D, Zheng S, Wada T, Xie W, Li Y. (2010) Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma. Mol Endocrinol, 24 (5): 923-9. [PMID:20203100]

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