il-17

IL-17 modulator 4 is a prodrug of IL-17 modulator 1 which is an efficacious modulator of IL-17.

IL-17 modulator 3 (US20200247785A1) is a chemical compound that acts as an IL-17 modulator. It has potential applications in researching inflammation, cancer, and autoimmune diseases.

IL-17 Modulator 1 (disodium) is a potent, orally active compound, known for its high efficacy in modulating IL-17. This compound is extensively utilized for researching various diseases such as psoriasis, ankylosing spondylitis, and psoriatic arthritis[1].

IL-17 modulator 5 is a IL-17 inhibitor, with an IC 50 of 1 nM .

(R)-IL-17 modulator 4 is the R-configured form of IL-17 modulator 4 and is a prodrug of IL-17 modulator 1. IL-IL-17 modulator 1 is a potent, orally active IL-17 modulator.

IL-17 modulator 4 sulfate is a prodrug of IL-17 modulator 1 . IL-17 modulator 1 is an orally active, highly efficacious IL-17 modulator.

Dersalazine (Dersalazine Free Base), an inhibitor of platelet-activating factor, exerts intestinal anti-inflammatory activity in different rodent types of colitis by down-regulating IL-17 expression, with potential efficacy in patients with ulcerative colitis.

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.

Vidofludimus (SC12267) (4SC-101, SC12267) is a novel small molecule inhibitor of dihydroorotate dehydrogenase (DHODH).

ML604440 is a cell permeable proteasome β1i (LMP2) subunit inhibitor.

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

Efineptakin alfa (NT-17), a long-acting recombinant human interleukin-7 (IL-7), promotes the proliferation and survival of CD4+ and CD8+ cells in both humans and mice. It has applications in glioblastoma research [1].

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.

Resolvins are a group of polyhydroxylated metabolites of docosahexaenoic acid (DHA) found in the inflammatory exudates of aspirin-treated experimental animals. 17(R)-HDHA is the primary oxygenation product of DHA when exposed to aspirin-inhibited cyclooxygenase-2. 17(R)-HDHA serves as a precursor to resolvins and has intrinsic biological activity, such as the inhibition of TNFα-induced IL-1β expression in human glioma cells.

NLRP3-IN-17 is a potent, selective, and orally active inhibitor of the NLRP3 inflammasome, demonstrating an IC50 of 7 nM. It effectively inhibits NLRP3-dependent IL-1β secretion in mice, making it a valuable compound for research into chronic inflammatory diseases [1].

Interphotoreceptor retinoid-binding protein (651-670) (IRBP651-670), a peptide fragment of retinoid-binding protein 3 (also known as IRBP), plays a crucial role in the visual cycle by facilitating the transport of retinol and retinal between photoreceptor cells and the retinal pigment epithelium. This transport is essential for the regeneration of pigments necessary for vision. When administered at a dose of 300 µg/animal, IRBP651-670 induces autoimmune uveoretinitis in C57BL/6 mice, a model possessing the H-2b haplotype. This immunization leads to increased levels of ocular cytokines including IL-1β, IL-6, IL-17, TNF-α, and IFN-γ, promotes immune cell infiltration into the eye, and results in photoreceptor cell damage.

ARN-6039 is an orally available inverse agonist of RORγ for Autoimmune Neuroinflammatory Demyelinating Disease. The activity of ARN-6039 against RORγ was demonstrated in a RORγ-activated IL-17A Prom/LUCPorter assay in HEK 293 cells (360 nM) and in IL-17 r

Netakimab, an anti-IL-17 monoclonal antibody, is utilized in the research of ankylosing spondylitis, psoriatic arthritis, and moderate-to-severe plaque psoriasis [1] [2].

AMS-17 is a potent NLRP3 inhibitor, which effectively suppresses microglia activation both in vitro and in vivo. Additionally, AMS-17 exhibits inhibitory effects on various cytokines, such as caspase-1, TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS), in N9 cells. Given these properties, AMS-17 holds promise as a valuable tool for investigating inflammation-associated neurological disorders [1].

Y-320 is a new phenylpyrazoleanilide immunomodulator.

(±)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).

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)

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. 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.

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.

Anti-inflammatory agent 17 an orally active anti-inflammatory agent, demonstrates potent efficacy in inhibiting the release of IL-6 and TNF-α without causing cytotoxicity in in vitro experiments. Furthermore, in vivo studies confirm its anti-inflammatory activity. Given its attributes, Compound 17 holds promise for investigating Acute lung injury (ALI) [1].

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.

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.

CK-17 is an interleukin-1 antagonist and an IL-1 blocker, which inhibits fibroblast proliferation in a concentration-dependent manner.

Risankizumab (BI 655066) is a humanized IgG monoclonal antibody (Kd <10 pM) targeting the IL-23 p19 subunit. Risankizumab 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(R)-Resolvin D3 (17(R)-RvD3) is an aspirin-triggered epimer of resolvin D3, produced from docosahexaenoic acid (DHA) through the action of COX-2 in the presence of aspirin, via a 17(R)-hydroperoxy DHA (17(R)-HDHA) intermediary. Identified in mouse inflammatory exudates, 17(R)-RvD3 notably inhibits the transmigration of isolated human polymorphonuclear cells (PMNs) and fosters the efferocytosis of apoptotic PMNs by macrophages. Furthermore, in a mouse model of zymosan-induced peritonitis, 17(R)-RvD3 administration (10 ng/animal) significantly curtails neutrophil infiltration into the peritoneal cavity and modulates cytokine levels by reducing IL-6 and increasing IL-10 in the inflammatory exudate. It engages GPR32, evidenced by activation in a β-arrestin reporter assay and augments phagocytosis more effectively in CHO cells overexpressing GPR32 compared to controls. Additionally, 17(R)-RvD3 enhances the clearance of etoposide-induced tumor cell debris by monocyte-derived macrophages in H460 human lung carcinoma.

AKP-11 is a sphingosine-1-phosphate receptor 1 (S1P1) agonist with an EC50 of 0.047 μM for [35S]GTPγS binding to CHO-K1 cell membranes expressing human S1P1. It reduces S1P1 surface expression and enhances Akt and ERK phosphorylation in CHO cells with S1P1-HA at a 100 nM concentration. At doses of 1.3 and 3 mg/kg, AKP-11 lowers IFN-γ and IL-17 protein levels in the spinal cord and mitigates disease severity in a rat experimental autoimmune encephalomyelitis (EAE) model. Additionally, it decreases peripheral total lymphocyte and specific T cell subsets (CD4+, CD8+, and CD26L+ T cells) counts in both EAE rats and healthy controls at a 1.3 mg/kg dosage.

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 3 is a potent, selective and orally active inverse agonist of RORγ(EC50s of 0.22 μM and 0.15 μM for hRORγ and RORγt (human IL-17 cells), respectively).

Ixekizumab (LY2439821) is a humanized IgG4 monoclonal antibody that selectively binds and neutralizes interleukin IL-17A with a Kd value of <3 pM.Ixekizumab blocks the binding of IL-17A to IL-17RA but not to other IL-17 family members.Ixekizumab is used for the treatment of moderate to severe plaque psoriasis, psoriasis, arthritis and psoriasis. arthritis, and psoriasis.

BMS-986251 is a potent and specific RORγt inverse agonist that exerts its action via oral administration. It shows an EC 50 of 12 nM for RORγt GAL4. In human whole blood assay, BMS-986251 effectively inhibits IL-17 with an EC 50 of 24 nM. Furthermore, BMS-986251 exhibits strong therapeutic effects in mouse acanthosis and Imiquimod-induced models, which are commonly used preclinical models for psoriasis.

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.