Th17

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].

GSK-J4 (GSK J4 HCl) is a cell permeable prodrug of GSK-J1, a dual inhibitor of the H3K27me3/me2 demethylases JMJD3/KDM6B and UTX/KDM6A (IC50=8.6/6.6 μM). GSK-J4 induces endoplasmic reticulum stress-related apoptosis.

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.

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.

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

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).

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

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

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.

BTH1704 is a human monoclonal antibody targeting MUC1. It facilitates the killing of iC3b-opsonized tumor cells by leukocytes triggered by PGG. BTH1704 is applicable in studies on pancreatic cancer and breast cancer.

ROR agonist-1 is a potent and orally bioavailable inverse agonist of the retinoic acid receptor-related orphan receptor C2 (RORC2), demonstrating inhibition of IL-17A production from human primary TH17 cells with a pIC50 of 7.5.

Brezivaptan (Brezivaptanum; TH1773; TS-121) is an antagonist of the vasopressin receptor (antidiuretic hormone receptor).

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.

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.

MS402 is a novel BD1-selective BET BrD inhibitor.

trans-Ned 19 is a nicotinic acid adenine dinucleotide phosphate (NAADP) antagonist and two-pore channel (TPC) blocker. It binds with high affinity to the NAADP receptor to inhibit NAADP-dependent lysosomal/endolysosomal calcium release without affecting IP3 or cADPR-mediated calcium signaling pathways. Functionally, trans-Ned 19 inhibits glucose-induced calcium oscillations in pancreatic islets and low histamine concentration-induced endothelium-dependent vasodilation, and reduces Ebola virus infection of host cells. In immunomodulation, NAADP signaling blockade by trans-Ned 19 promotes the conversion of mouse Th17 cells to regulatory T cells (Tregs) and shows protective effects in intestinal inflammation models.

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

Trehalose 6-behenate is a vaccine adjuvant that skews the immune response towards Th1/Th17.

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.

AJI-100 serves as a dual-target inhibitor, effectively blocking Aurora kinase A and JAK2, with respective IC50 values of 12.7 nM and 18.5 nM. It inhibits T cell mitosis and cell polarity by directly targeting Aurora kinase A and reduces STAT3 phosphorylation by inhibiting JAK2 activation, consequently diminishing the differentiation of TH1 and TH17 cells. This compound is utilized in researching immune response regulation and the prevention of graft-versus-host disease (GVHD).

AJI-214 functions as a dual-target inhibitor that specifically blocks Aurora kinase A and JAK2. By directly inhibiting Aurora kinase A, AJI-214 prevents mitotic progression and cell polarity in T cells while concurrently suppressing JAK2 activation to reduce STAT3 phosphorylation. This inhibition decreases the differentiation of TH1 and TH17 cells. AJI-214 is utilized in research focused on the modulation of immune responses and the prevention of graft-versus-host disease (GVHD).

4-Octylphenol is an endocrine disruptor with gender-specific effects on male germ cells, significantly reducing the mitotic index and the number of spermatogonia. It also causes inflammatory damage in the gills of carp by activating the complement system through the C3a/C3a receptor (C3a/C3aR) axis and C5a/C5a receptor 1 (C5a/C5aR1) axis. Furthermore, 4-Octylphenol induces immune suppression by disrupting the balance between helper T (Th) cells 1/Th2 and regulatory T (Treg)/Th17 cells, and triggers inflammatory damage through the Toll-like receptor 7 (Toll-like Receptor (TLR))/inhibitor κBα/nuclear factor κB (TLR7/IκBα/NF-κB) pathway.

RORγt inverse agonist 35 (Compound 22) is an RORγt inverse agonist with an IC50 of 1.51 μM. It significantly inhibits Th17 differentiation and pro-inflammatory characteristics in human CD4+ T cells. This compound can be utilized for research on Th17-driven autoimmune diseases, such as psoriasis, multiple sclerosis, and inflammatory bowel disease (IBD).

ITK-IN-6 is a potent and selective ITK inhibitor (Kd = 387 nM). It binds directly to the ITK kinase domain. This compound prevents the release of pro-inflammatory cytokines and the activation and differentiation of Th2 and Th17 cells. ITK-IN-6 improves asthma progression by reducing inflammatory cell infiltration, mucus production, and IgE generation. It significantly inhibits airway inflammation and is used in asthma research.