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Metabolism

ATP Citrate Lyase

(11)

Acetyl-CoA Carboxylase

Amino Acids and Derivatives

Angiotensin-converting Enzyme (ACE)

Endogenous Metabolite

Glutathione Peroxidase

(36)

HIF/HIF Prolyl-Hydroxylase

Indoleamine 2,3-Dioxygenase (IDO)

(33)

Isocitrate Dehydrogenase (IDH)

Mitochondrial Metabolism

(85)

N-Acetylglucosaminyltransferase

Procollagen C Proteinase

(1)

Prolyl Endopeptidase (PREP)

Reactive Oxygen Species

Serine/threonin kinase

(47)

Stearoyl-CoA Desaturase (SCD)

ROR

The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors. There are three forms of ROR, ROR-α, -β, and -γ and each is encoded by a separate gene RORA, RORB, and RORC respectively. The RORs are somewhat unusual in that they appear to bind as monomers to hormone response elements as opposed to the majority of other nuclear receptors which bind as dimers. They bind to DNA elements called ROR response elements (RORE).

Filter HomeSignaling PathwaysMetabolismROR

Cholesterol

T076057-88-5

Cholesterol (cholesteryl alcohol) is a natural product that is the major sterol in mammals and an agonist of estrogen-related receptor α (ERRα). Cholesterol is widely found in the cell membranes of animals and is also used in the synthesis of several important hormones and bile acids.

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Nobiletin

T2834478-01-3

Nobiletin (Hexamethoxyflavone) is a natural polymethoxylated flavone isolated from citrus peels with anti-inflammatory and anti-tumor activities. Nobiletin is practically insoluble (in water) and an extremely weak acidic compound (based on its pKa).

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3-Oxo-5β-cholanoic acid

T135021553-56-6

3-Oxo-5β-cholanoic acid (Dehydrolithocholic acid) is a bile acid metabolite that inhibits TH17 cell differentiation by directly binding to the transcription factor RORγt with a Kd of 1.13 μM.

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GSK805

T73881426802-50-7

GSK805 is a potent, orally bioavailable and CNS-penetrant RORγt inhibitor.

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Neoruscogenin

T3S125117676-33-4

1. Neoruscogenin represents a universal pharmacological tool for RORα research due to its specific selectivity profile versus other nuclear receptors.

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Bevurogant

T392501817773-66-2

Bevurogant is an antagonist of RORγt receptor and can be used in studies about the treatment of chronic inflammatory diseases.

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ML 209

T375871334526-14-5In house

ML-209 is an antagonist of retinoic acid receptor-related orphan receptor γt (RORγt; IC50= 1.1 μM in a reporter assay).1It inhibits RORγt-induced transcription in HEK293T cells expressing the human receptor (IC50= 300 nM). ML-209 inhibits RORγt-dependent differentiation of isolated na?ve cord blood human CD4+T cells into Th17 T helper cells.

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T0901317

T6690293754-55-9

T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively; it inhibits nuclear factor κB (NF κB).

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SR1078

T45941246525-60-9

SR1078 is an agonist of retinoic acid receptor-related orphan receptor (ROR)α γ.

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SR3335

T5160293753-05-6

SR3335 (ML 176) is a selective inverse agonist of RORα that competitively inhibits the binding of 25-hydroxycholesterol to the ligand binding domain (Ki: 220 nM).

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GSK2981278

T40501474110-21-8

GSK2981278 (ROR gama modulator 1) is a highly potent and selective inverse agonist of retinoic acid receptor-related orphan receptor gamma (ROR gamma).

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Cedirogant

T96352055496-11-0

Cedirogant (ABBV-157) is an orally active, retinoid-related orphan receptor-γt (RORγt) inverse agonist used in psoriasis studies.

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XY101

T133622349368-16-5In house

XY101 is a selective, metabolically stable and orally available agonist of RORγ inverse(IC50 of 30 nM and a Kd of 380 nM).

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SR1001

T51631335106-03-0

SR 1001 is an inverse agonist for RORα/RORγ (Kis: 172/111 nM).

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SR0987

T4670303126-97-8

SR0987 is a RORγt agonist,

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S18-000003

T168322068119-11-7

S18-000003 is an effective orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t inhibitor (IC50: 29 nM). S18-000003 inhibits IL-17 production.

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XY018

T242131873358-87-2

XY018 is an orally available, selective and highly effective ROR-γ antagonist with antitumor activity, inhibits ROR-γ activity, inhibits tumor cell growth, and can be used to study drug-resistant prostate cancer.

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SR2211

T169291359164-11-6

SR2211 is a specific modulator and an inverse agonist of RORγ(IC50 = 320 nM, Ki = 105 nM).

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Cabozantinib hydrochloride

T51641817759-42-4

Cabozantinib hydrochloride (XL184) is a potent pan-tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt4 (IC50s: 0.035, 1.3, 4.6, 7 and 6 nM).

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Cintirorgon

TQ00072055536-64-4

Cintirorgon (LYC-55716) is a selective, oral agonist of RORγ, modulating gene expression in RORγ-expressing T lymphocyte immune cells.

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AZD-0284

T143692101291-07-8In house

AZD-0284 is an inverse agonist of the nuclear receptor RORγ. In development for the treatment of plaque psoriasis vulgaris and respiratory tract disorders[1].

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RORγt inverse agonist 13

T96232170477-75-3

RORγt inverse agonist 13 (Compound 3i) is a potent, orally active, and selective inverse agonist for RORγt with an IC50 of 63.8 nM, exhibiting improved drug-like properties[1].

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RORγt Inverse agonist 6

T127531887161-80-9

RORγt Inverse agonist 6 is an agonist of RORγt inverse. RORγt Inverse agonist 6 can be used in research on Th17-driven autoimmune diseases.

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TMP-778

T13172L11422171-08-1

TMP-778 is a selective inverse agonist of RORγt.

$223

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RORγt inverse agonist 31

T79470

RORγt inverse agonist 31 (14g) is a potent antagonist of the retinoic acid receptor-related orphan receptor γt (RORγt), with an inhibitory concentration (IC50) of 0.428 μM. It has shown efficacy in reducing Imiquimod-induced psoriasis severity in murine models [1].

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TMP920

T171081421837-45-7

TMP920 inhibits RORγt binding to the SRC1 peptide (IC50: 0.03 μM). TMP920 is a highly potent and selective RORγt antagonist.

$119

5 days

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TAK-828F

T130671854901-94-2

TAK-828F is a potent, selective, and orally available retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonist, with an IC50 of 1.9 nM and a reporter gene IC50 of 6.1 nM.

$3,170

10-14 weeks

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RORγt Inverse agonist 8

T127542079892-79-6

RORγt Inverse agonist 8 is a potent, selective, orally bioavailable RORγt inverse agonist (human RORγt-LBD) with an IC50 of 19 nM.

$1,670

6-8 weeks

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FM26

T113082407981-35-3

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

$1,970

8-10 weeks

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Vimirogant

T167871802706-04-2

Vimirogant is a RORγ inhibitor (Ki: <100 nM).

$2,270

10-14 weeks

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RORγt inverse agonist 14

T722522672496-70-5

RORγt inverse agonist 14 (8e) is a potent, selective, and orally active compound with an EC50 of 2.5 nM, demonstrating anti-inflammatory activity. It is utilized in the research of rheumatoid arthritis and psoriasis [1].

$1,770

8-10 weeks

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RORγ antagonist 1

T79464

RORγ antagonist 1 (compound 22), a potent derivative of betulinic acid, acts as an antagonist to RORγ with a dissociation constant (K D) of 0.18 μM. It demonstrates anti-proliferative effects in the HPAF-II pancreatic cancer xenograft model, inhibits the RAS MAPK and AKT mTORC1 signaling pathways, and triggers caspase-dependent apoptosis in pancreatic cancer cells [1].

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Zymostenol

T35321566-97-2

Zymostenol (5a-Cholest-8-en-3b-ol) is a RORγ agonist with an EC50 of 1 μM and serves as a late-stage precursor in cholesterol biosynthesis.

$263

35 days

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TMP780

T131721422053-03-9

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

$1,620

8-10 weeks

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A-9758

T102102055271-22-0

A-9758 is a RORγ ligand and selective RORγt inverse agonist (IC50: 5 nM) that effectively suppresses IL-17A release, Th17 differentiation, and Th17 effector function, significantly attenuating IL-23 driven psoriasiform dermatitis.