il-17 production

Y-320 is a new phenylpyrazoleanilide immunomodulator.

Brodalumab (AMG 827) is a human monoclonal IgG2 antibody targeting the interleukin 17 receptor (IL-17R), commonly used as an immunosuppressant in treating psoriasis.

1beta-Hydroxyalantolactone is a small molecular compound isolated from the flower head of the medicinal plant giant British flower, which can inhibit the expression of TNF-α, IL-17 and IFN-γ in cells, promote the secretion of TNF-α, IFN-γ and IL-17, and prevent and treat rheumatoid arthritis.

3-Hydroxykynurenamine, also known as 3-Hydroxy-L-kynurenamine or 3-HKA, is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1 NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction.This compound is unstable in powder form and other related salt forms are recommended.

Beclomethasone 17-propionate is a glucocorticoid that is the active metabolite of Beclomethasone dipropionate (BDP). As a glucocorticoid receptor (GR) agonist, 17-BMP has a 13-fold higher affinity than BDP and inhibits the production of pro-inflammatory cytokines, such as CXCL8, TNF-α, and IL-6, thus exerting an anti-inflammatory effect, and it is mainly used in the treatment of asthma and allergic rhinitis.

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.

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.

JAK3-IN-17 is an orally active JAK3 inhibitor with an IC50 of 14.56 nM. It demonstrates anti-inflammatory activity by inhibiting the production of IL-2 and IL-6 in a DNCB-induced mouse model of atopic dermatitis.

SB-505124 hydrochloride (SB505124 hydrochloride) is an orally available, selective and potent inhibitor of TGF-β type I receptors (ALK4, ALK5, ALK7) with IC50 values of 129 nM and 47 nM for ALK4 and ALK5, respectively. SB-505124 hydrochloride inhibits IL-6 production by synovial explants and reduces Th17 differentiation in mice by decreasing Il17a and Rorc gene expression and IL-17 protein production.SB-505124 hydrochloride is used in the study of colorectal cancer.

5J-4 is a potent a blocker of calcium release-activated calcium (CRAC) channel and store-operated calcium entry (SOCE). 5J-4 reduces the production of IL-17 and decreases the expression of RORα and RORγt.

C2 L-threo Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. It stimulates cholesterol efflux in CHO cells expressing the human ABCA1 receptor when used at a concentration of 10 μM, however, this efflux is 50% less than that stimulated by C2 ceramide . C2 L-threo Ceramide inhibits IL-4 production by 17% in EL4 T cells stimulated with phorbol 12-myristate 13-acetate when used at a concentration of 10 μM. It also induces cell cycle arrest in the G0 G1 phase and a 7-fold increase in sphingosine accumulation as well as inhibits growth of HL-60 leukemia cells.

IRAK4-IN-22 is a selective, orally active, potent IRAK4 inhibitor that acts on IRAK4 (IC50: 3 nM) and TAK1 (IC50: 17 nM). IRAK4-IN-21 exhibits potent inhibition of IL-23 production with an IC50 value of 0.10 μM. IRAK4-IN-21 can be used to study autoimmune diseases, such as plaque psoriasis and psoriatic arthritis.

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

GNE-3500 is a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist. Retinoic acid receptor-related orphan receptor C (RORc, RORγ, or NR1F3) is a nuclear receptor that plays a major role in the production of interleukin (IL)-17. Considerable efforts have been directed toward the discovery of selective RORc inverse agonists as potential treatments of inflammatory diseases such as psoriasis and rheumatoid arthritis. GNE-3500 possessed favorable RORc cellular potency with 75-fold selectivity for RORc over other ROR family members and >200-fold selectivity over 25 additional nuclear receptors in a cell assay panel. The favorable potency, selectivity, in vitro ADME properties, in vivo PK, and dose-dependent inhibition of IL-17 in a PK PD model support the evaluation of GNE3500 in preclinical studies (J. Med. Chem., 2015, 58 (13), pp 5308–5322)

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.

Risankizumab (BI 655066) is a humanized IgG monoclonal antibody (Kd <10 pM) targeting the IL-23 p19 subunit. It inhibits IL-17 production induced by human IL-23 in mouse splenocytes with an IC50 value of 2 pM. Risankizumab is used for the prevention and treatment of immune and inflammatory disorders such as psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis.

(±)17(18)-EpETE-Ethanolamide, an ω-3 endocannabinoid epoxide, originates from eicosapentaenoic ethanolamide (EPEA) through cytochrome P450 (CYP) epoxygenases action and is decomposed by soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FA, AH). Its endogenous synthesis occurs in LPS-stimulated and EPEA-supplemented BV-2 microglia cells, a process inhibited by the CYP inhibitor ketoconazole. This compound mitigates IL-6 and nitrite levels while enhancing IL-10 production following LPS exposure in BV-2 microglia. At a dose of 50 µM, it prevents platelet aggregation caused by arachidonic acid but not that triggered by ADP, collagen, or ristocetin. Additionally, it facilitates the dilation of constricted bovine coronary arteries (ED50= 1.1 µM) and blocks VEGF-driven tubulogenesis in human microvascular endothelial cells (HMVECs).