th17

GSK805 is a potent, orally bioavailable retinoid-related orphan receptor gamma t (RORγt) inverse agonist that interacts with the receptor's putative ligand binding domain without exerting significant effects on DNA binding

GSK-J4 (GSK J4 HCl) is a potent H3K27me3 demethylase inhibitor, with IC50s of 8.6 μM and 6.6 μM towards KDM6B and KDM6A respectively. It is the first selective inhibitor of the H3K27 histone demethylase JMJD3 and UTX with IC50 of 60 nM in a cell-free assay and inactive against a panel of demethylases of the JMJ family.

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.

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].

TH1760 (MKB) is an inhibitor of NUDIX-type 15 (NUDT15, IC50= 25 nM). TH1760 can sensitize cells to 6-thioguanine by increasing the accumulation of 6-thio- (d) GTP in nucleic acids. TH1760 can enhance the anti-leukemia effect of thiopurine.

SGC-CBP30 is an effective CREBBP/EP300 inhibitor (IC50: 21/38 nM).

MS402 is a novel BD1-selective BET BrD inhibitor.

Spesolimab (BI 655130) is an anti-interleukin-36 receptor antibody. IL-36 plays an important role in the immune system and is associated with a reduction in biomarkers associated with congenital Th1/Th17 and neutrophil pathways. Spesolimab can be used to study systemic pustular psoriasis, palmar and plantar impetigo (PPP), and atopic dermatitis.

Trehalose 6-behenate is a Th1/Th17 skewing vaccine adjuvant.

GSK-J4 Hydrochloride (GSK J4 HCl) is a cell permeable, potent and selective histone demethylase(JMJD3 )inhibitor. is an ethyl ester derivative of the GSK-J1 with an IC50 value greater than 50 μM in vitro.

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

Isoformononetin shows fungitoxic activity against Cladosporium sphaerospermum; it also has immunomodulatory activity, it inhibits the differentiation of Th17 cells and B-cell lymphopoesis to promote osteogenesis in estrogen-deficient bone loss conditions.

Ciglitazone (ADD 3878) is a potent and selective PPARγ agonist (EC50: 3 μM) and oral hypoglycemic agent. Ciglitazone inhibits proliferation and differentiation of th17 cells, decreases insulin levels, vascular endothelial growth factor production and blood pressure, and induces cell cycle arrest in gastric cancer cells. Selegiline induces apoptosis in opossum kidney epithelial cells and activates nuclear translocation of p38 MAPK and apoptosis-inducing factor (AIF). Ciglitazone exhibits hypoglycaemic activity in animal models of obesity and hyperglycaemia.

RORγt inverse agonist 28 is a potent RORγt inverse agonist. RORγt inverse agonist 28 regulates the differentiation of Th17 cells and inhibits the production of IL-17. RORγt inverse agonist 28 has shown research potential in inflammatory and autoimmune diseases.

JAK1/TYK2-IN-3 is a selective, potent, orally active dual inhibitor of TYK2 (IC50: 6 nM) and JAK1 (IC50: 37 nM).JAK1/TYK2-IN-3 selectively acts on both JAK2 and JAK3 with IC50 values of 140 nM and 362 nM.JAK1/TYK2 -IN-3 regulates the expression of TYK2/JAK1-related genes and the formation of Th1, Th2 and Th17 cells to exert its anti-inflammatory activity.

AHR agonist 4 (compound 24e), as an Aryl hydrocarbon receptor (AHR) agonist, modulates the immune equilibrium between Th17/22 and Treg cells. It is a lead compound under investigation for anti-psoriasis drugs and demonstrates efficacy in mitigating imiquimod (IMQ)-induced psoriasis-like skin lesions [1].

Acetyl-Exenatide, an acetylated derivative of Exenatide, mirrors insulin's functionality and is utilized in type 2 diabetes research. It promotes Th17 differentiation, inhibits Tregs differentiation, and downregulates PI3K/Akt/FoxO1 phosphorylation [1].

7β,27-dihydroxy Cholesterol is an oxysterol and agonist of retinoic acid receptor-related orphan receptor γ (RORγ) and RORγt. [1] It activates RORγ- or RORγt-dependent signaling with EC50 values of 691 and 1,045 nM, respectively, in reporter assays using HEK293T cells expressing the recombinant human receptors. 7β,27-dihydroxy Cholesterol is selective for RORγ and RORγt over a panel of eight additional nuclear receptors at 30 µM. It increases IL-17A production in Th17-polarized isolated human na ve CD4+ T cells when used at a concentration of 300 nM. 7β,27-dihydroxy Cholesterol (60 mg/kg) increases IL-17A production in isolated mouse γδ T cells stimulated with 12-myristate 13-acetate and ionomycin .

RORγt agonist 2 is a potent agonist of RORγt. RORγt agonist 2 induces Th17 cell differentiation, increases levels of pro-inflammatory cytokines and thus enhances lymphocyte cytotoxicity. rorγt agonist 2 exhibits an inhibitory effect on the production of regulatory T cells and is able to suppress immune responses.

RORγt agonist 3 is a potent agonist of RORγt. RORγt agonist 3 induces Th17 cell differentiation, increases levels of pro-inflammatory cytokines and thus increases lymphocyte cytotoxicity. rorγt agonist 3 blocks the production of regulatory T cells and suppresses the immune response.

ER819762, an antagonist of the prostaglandin E2 EP4 receptor, inhibits Th1 differentiation and Th17 expansion.

RORγt inverse agonist 26, a potent reverse agonist of RORγt, effectively modulates Th17 cell differentiation and suppresses IL-17 production. This compound shows promising potential for researching inflammation and autoimmune diseases.

Vimirogant (VTP-43742) hydrochloride is an orally active, selective RORγt inhibitor (IC50: 17 nM, Ki: 3.5 nM) that is more than 1000 times more selective than RORα and RORβ. Vimirogant hydrochloride inhibits Th17 differentiation and IL-17A secretion in mouse spleen cells with an IC50 value of 57 nM and does not affect the differentiation of Th1, Th2 or Treg cells.

FASN-IN-5 (example 11) is a FASN inhibitor that can be used in studies of TH17 or CSF1-mediated diseases or disorders (e.g. cancer, immune disorders, obesity).

JNJ-61803534 is a potent, orally active RORγt inverse agonist, demonstrating anti-inflammatory activity through inhibition of IL-17A production in human CD4+ T cells under Th17 differentiation conditions, with an IC50 of 9.6 nM.

SR1555 is a selective RORγ inverse agonist that inhibits the development and function of TH17 cells, a subset of T cells that have been involved in the pathology of several autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

A-9758 is a RORγ ligand and a selective RORγt inverse agonist (IC50: 5 nM) and exhibits robust potency against IL-17A release. It is effective in suppressing both Th17 differentiation and Th17 effector function. A-9758 significantly attenuates IL-23 drive

SHR0302 (ARQ252) is a JAK inhibitor that binds JAK1 with stronger affinity than others (Selectivity for JAK1 is more than 10 times for JAK2, 77 times for JAK3, 420 times for Tyk2).

Lithocholic acid 3-sulfate disodium (Sulfolithocholic acid disodium) acts as a RORgammat ligand and inhibits Th17 cell differentiation.Lithocholic acid 3-sulfate disodium is a sulfated product of lithocholic acid (LCA) and induces a decrease in arterial blood pressure. Lithocholic acid 3-sulfate disodium is a sulfated product of lithocholic acid (LCA) that induces cellular damage.

BET BD2-IN-1 (compound 45) is a potent, selective inhibitor of BET BD2, exhibiting an IC50 value of 1.6 nM. It suppresses Th17 cell differentiation through the reduced activation of STAT3 and NF-κB, making it relevant in research on psoriasis and inflammatory bowel disease (IBD) [1].

ROR agonist-1 is a potent and orally bioavailable the retinoic acid receptor-related orphan receptor C2 (RORC2) inverse agonist(inhibition of IL-17A production from human primary TH 17 cells with a pIC50 of 7.5).

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

TMP778 is an effective and selective RORγt inverse agonist (IC50: 7 nM in FRET assay).