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

IL-4 inhibitor is an inhibitor of IL-4.1It binds to IL-4 with a Kdvalue of 1.8 μM and inhibits IL-4 activity in a cell-based reporter assay (EC50= 1.81 μM). It is selective for IL-4 over IL-13 (EC50= 18.2 μM). IL-4 inhibitor inhibits IL-4-induced STAT6 phosphorylation in THP-1 monocytes (EC50= 3.1 μM), indicating inhibition of the IL-4-JAK1-STAT6 signaling pathway.

(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.

RV01 is a novel quinoline-substituted analogue of resveratrol that inhibits DNA damage, reduces ethanol-induced acetaldehyde dehydrogenase (ALDH2) mRNA expression, and has hydroxyl radical scavenging activity. rV01 reduces iNOS expression and has anti-neuroinflammatory effects. rV01 reduces tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion. RV01 reduced tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) mRNA levels and secretion, inhibited lps-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, decreased toll-like receptor 4 (TLR4) protein expression, and inhibited lps-induced activation of mitogen-activated protein kinase (MAPK) and nuclear transcription factor-кB (NF-кB) signaling pathways.

4-Methylesculetin (Methylesculetin) is one of the coumarin derivatives with great anti-oxidant and anti-inflammatory activities.

BI-69A11 ((E)-3-(1H-Benzo[d]imidazol-2-yl)-1-(6-chloro-2-hydroxy-4-phenylquinolin-3-yl)prop-2-en-1-one) is a dual AKT and NFkB pathway inhibitor. It enhances the susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt.

Ataquimast inhibits IL-5 secretion along with that of TNF-a, IL-4 and GM-CSF from human cells.

Icaritin (Anhydroicaritin) has hormone regulation activity and cardiovascular function improvement activity. Icaritin has anticancer activity, can induce S phase arrest and apoptosis, inhibit ENKL cell proliferation. Icaritin has anti-multiple myeloma activity, mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. Icaritin at low concentration (4 or 8 μMol/L) can promote rat chondrocyte proliferation and inhibit cell apoptosis, while the effect of Icaritin on rat chondrocyte at high concentration was reversed.

Ginsenoside-F3 has immunoenhancing activity by regulating production and gene expression of type 1, type 2 cytokines in murine spleen cells. Ginsenoside-F3 enhances the NF-kappaB DNA binding activity induced by ConA in murine spleen cells (10 μM).

Romilkimab (SAR156597) is a chimeric humanized immunoglobulin (Ig) antibody designed to specifically target interleukins 4 and 13 (IL-4 and IL-13) [1].

Stapokibart (CM310), a humanized monoclonal antibody, selectively binds to IL-4Rα, inhibiting the cytokines IL-4 and IL-13 from interacting with their shared co-receptor subunit, IL-4Rα. This compound demonstrates cross-species reactivity by interacting with IL-4Rα in humans, cynomolgus monkeys, and rats [1].

C12 Galactosylceramide is a bioactive sphingolipid. It inhibits IL-4 production by 53.84% in EL4 T cells when used at a concentration of 10 μM. C12 Galactosylceramide reduces the growth of human papillomavirus type 16-associated tumors in mice and reduces tumor recurrence following surgical removal or chemotherapy. It also reduces natural killer T cell activity, delays the onset of proteinuria, and improves survival in a mouse model of systemic lupus.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

JC2-11 is an inhibitory compound for inflammation.JC2-11 inhibits the recruitment domain-containing proteins NLRC 4, atypical in melanoma 2 (AIM 2) and atypical (NC) inflammatory vesicles by disrupting reactive oxygen species (ROS) production and caspase-1 activity.JC2-11 reduces caspase-1 (p20) secretion, gasdermin D (GSDMD) cleavage, IL-1β and lactate dehydrogenase (LDH) activity in inflammatory vesicles. JC2-11 reduced caspase-1 (p20) secretion, gasdermin D (GSDMD) cleavage, IL-1β and lactate dehydrogenase (LDH) release from inflammatory vesicles.

Rademikibart (CBP-201) is a human monoclonal antibody selective for IL-4Rα, exhibiting strong affinity with a KD of 20.7 pM for human IL-4Rα epitopes, without cross-reactivity to IL-4Rα from other species. It effectively inhibits IL-4 and IL-13-induced STAT6 signaling, TF-1 cell proliferation, and TARC production in PBMCs, showing promise for investigating moderate-to-severe Th2 inflammatory diseases [1].

Rolinsatamab is a fully humanized selective monoclonal antibody that is a potent dual inhibitor of IL-4 and IL-13. Rolinsatamab chimeric antigen receptor sequence T cells. Rolinsatamab can be used to prevent and treat immune diseases.

IRAK4-IN-7 (CA-4948) is a selective and potent IRAK4 kinase inhibitor with in vivo activity in a TLR4-induced cytokine release model.

IRAK4-IN-4 (compound 15) inhibits cyclic GMP-AMP synthase (cGAS) with an IC50 of 2.1 nM.IRAK4-IN-4 is an interleukin-1 receptor–associated kinase 4 (IRAK4) inhibitor, has an IC50 of 2.8 nM.

Glaucine has antitussive, antioxidative potential and antiviral activities, it may be an anti-arthritic agent, it can enhance LPS and zymosan-induced IL-10 production. Glaucine can inhibit the migration and invasion of human breast cancer cells by MMP-9 i

Compound 14a (P2X7 receptor antagonist-4) is a P2X7R antagonist with IC50 values of 64.7 nM in humans and 10.1 nM in mice. It inhibits the activation of the NLRP3 inflammasome, which subsequently reduces the expression of caspase-1, gasdermin D, IL-1β, and IL-18 in the kidneys of mice with sepsis-induced damage [1].

Pascolizumab (SB-240683) is a humanized monoclonal antibody against IL-4. Pascolizumab has asthmatic effects and can be used to study allergic rhinitis.

IRAK-4 protein kinase inhibitor 2 is a potent interleukin-1 receptor-associated kinase-4 (IRAK-4) inhibitor(IC50 = 4 μM).

C18 Phytoceramide (t18:0/18:0) (Cer(t18:0/18:0)) is a bioactive sphingolipid found in S. cerevisiae, wheat grains, and the stratum corneum layer of mammalian epidermis. Cer(t18:0/18:0) is composed of a phytosphingosine backbone amine-linked to a C18 fatty acid chain. Cer(t18:0/18:0) has a role in regulation of apoptosis, cell differentiation, proliferation of smooth muscle cells, and inhibition of the mitochondrial respiratory chain. It also inhibits expression of the allergic cytokines IL-4, TNF-α, and transcription factors c-Jun and NF-κB in histone-stimulated murine skin tissue. Formulations containing cer(t18:0/18:0) have been used used in cosmetics as a skin protectants as they reduce water loss to prevent epidermal dehydration and irritation.

β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It induces migration of monocytes in vitro when used at a concentration of 10 nM but does not affect migration of neutrophils and eosinophils. β-Defensin-4 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-4 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose. It also inhibits growth of E. coli, P. aeruginosa, and S. aureus with lethal concentration (LC) values of 5, 12, and 15 μM, respectively, of S. carnosus (MIC = 4.5 μg/ml), and of C. albicans with a minimum fungicidal concentration (MFC) value of 7.5 μM.

α-Galactosylceramide analog 8 (α-GalCer analog 8) is a triazole derivative of α-galactosylceramide. [1] It increases IL-2 secretion by DN32.D3 NKT hybridoma cells when co-cultured with CD1d-transfected RBL cells pre-loaded with α-GalCer analog 8 at a concentration of 32 ng/ml. α-GalCer analog 8 (32 ng/ml) induces IL-4 secretion to a greater extent than the synthetic α-GalCer KRN 7000 in mouse splenocytes in vitro and in mouse serum following administration of a 1 µg per animal dose, indicating a Th2 response.

PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC50= 31 nM).1It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.2,3PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer's disease.4 1.March, D.R., Proctor, L.M., Stoermer, M.J., et al.Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activityMol. Pharmacol.65(4)868-879(2004) 2.Jain, U., Woodruff, T.M., and Stadnyk, A.W.The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10Br. J. Pharmacol.168(2)488-501(2013) 3.Staab, E.B., Sanderson, S.D., Wells, S.M., et al.Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthmaInt. Immunopharmacol.21(2)293-300(2014) 4.Fonseca, M.I., Ager, R.R., Chu, S.-H., et al.Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseJ. Immunol.183(2)1375-1383(2009)

Dupilumab (REGN-668) is a systemic immunomodulator for AD. Dupilumab is a fully human monoclonal antibody against the alpha subunit of the interleukin-4 receptor, which inhibits downstream signaling of IL-4 and IL-13 and has been shown to improve atopic dermatitis.

Lacto-N-neotetraose (LNnT), an endogenous metabolite, inhibits TNF-α-induced IL-8 secretion in immature epithelial cells, exhibits anti-inflammatory activity, and enhances wound closure [1] [2] [4].

p38 MAPK inhibitor (IC50 = 0.38 μM). Inhibits the release of IL-1β and TNF-α in a peripheral blood mononuclear cell (PBMC) assay (IC50 values are 0.039 and 0.16 μM respectively). Laufer et al (2003) Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J.Med.Chem. 46 3230 PMID:12852754 |Kammerer et al (2007) Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl)-amine), a 4-pyridinylimidazole-type p38 mitogen-activated protein kinase inhibitor. Drug Metab.Dispos. 35 875 PMID:17344341

AcylCoA:cholesterol acyltransferase (ACAT) is an intracellular cholesteryl ester synthase tied closely to the absorption of dietary cholesterol. Oleyl analide (OA) is a weak inhibitor of acylCoA:cholesterol acyltransferase (ACAT) with an IC50 of 26 μM. OA and the related glyceride dioleoyl phenylamino propane 1,2-diol have been linked to a syndrome of eosinophilia, excessive T-cell activation, and elevated interleukin-4 (IL-4), soluble IL-2R, and IL-5. The clinical consequences are an acute pulmonary inflammatory reaction followed by chronic neuropathy, myalgia, and autoimmune connective tissue disease, generally referred to as toxic oil syndrome (TOS). Aniline-denatured cooking oil is a source of OA associated with TOS.

Fevipiprant (NVP-QAW039) is a selective, potent, reversible competitive CRTh2 antagonist.

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

AZ1495 is an oral active inhibitor of Interleukin-1 receptor associated kinase 4 (IRAK4), with IC50 values of 5 nM and 23 nM for IRAK4 and IRAK1, respectively. Which Shows activity in treatment of mutant MYD88L265P diffuse large B-cell lymphoma (DLBCL).

1. Monotropein (Monotropeine) has antinociceptive action. 2. Monotropein has anti-apoptosis and anti-catabolic activity in chondrocytes. 3. Monotropein has anti-inflammatory action by inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis. 4. Monotrope ininhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages.

Terminolic acid (2α,6β,23-trihydroxyl oleanolic acid) is a pentacyclic triterpenoid glucoside isolated from Combretum racemosum, can inhibit the pro-inflammatory cytokines by binding to receptor active site of IL-1β and IL-6, and enhance anti-inflammatory cytokines by binding to IL-4 receptor binding sites. It also exhibits moderate antibacterial activity.

EP4 antagonist 14 is a prostaglandin E2 receptor subtype EP4 antagonist, demonstrating an IC50 of 1.1 nM in a HEK293 human receptor reporter assay and blocking β-arrestin recruitment due to PGE2 with an IC50 of 0.9 nM. At 10 µM, it reduces PGE2-stimulated mRNA levels of Il-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C) motif ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase-1 (Arg1) in RAW 264.7 macrophages. When used at 30 mg/kg per day alongside anti-PD-1 antibodies, it curbs tumor growth and enhances CD8+ T cell infiltration in tumors using a CT26 murine colon cancer model.

NCI 126224, a toll-like receptor 4 (TLR4) antagonist, demonstrates selective inhibition of nitric oxide (NO) production in RAW 264.7 macrophages, triggered by the TLR4 agonist LPS (IC50 = 0.31 µM), as opposed to minimal effects on NO production induced by agonists for TLR7/8 (R-848), TLR1/2 (Pam3CSK4), and TLR3 (poly(I:C)). Nevertheless, it also effectively inhibits NO production initiated by the TLR2/6 agonist FSL-1 at an IC50 of 0.6 µM in the same cell line. Moreover, NCI 126224 suppresses LPS-induced NF-κB activity in BV-2 microglial cells and reduces LPS-triggered increases in IL-1β and TNF-α levels in RAW 264.7 macrophages with IC50 values of 5.92, 0.42, and 1.54 µM, respectively.

Theophylline (1,3-Dimethylxanthine) sodium glycinate is a potent inhibitor of phosphodiesterase (PDE) that inhibits PDE3 activity to relax airway smooth muscle. Theophylline sodium glycinate can be used for the research of asthma and chronic obstructive pulmonary disease (COPD). Theophylline sodium glycinate is also an adenosine receptor antagonist and histone deacetylase (HDAC) activator. Theophylline sodium glycinate has anti-inflammatory activity by increasing IL-10 and inhibiting NF-κB nucleus import. Theophylline sodium glycinate induces apoptosis [1] [2] [3] [4] [5].

C4 Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. [1] [2] [3] It inhibits IL-4 production by 16% in EL4 T cells stimulated with phorbol 12-myristate 13-acetate when used at a concentration of 10 μM. [1] C4 Ceramide is cytotoxic to SK-BR-3 and MCF-7/Adr breast cancer cells (IC50s = 15.9 and 19.9 μM, respectively). [2] C4 Ceramide also increases maturation and stability of cystic fibrosis transmembrane conductance regulator (CFTR) proteins bearing the F508 deletion (F508del) mutation, enhances cAMP-activated chloride secretion, and suppresses secretion of IL-8 in primary epithelial cells isolated from patients with cystic fibrosis.[3]

Luteolin-4'-O-glucoside (Luteolin-4-o-glucoside) is an inhibitor of IL-5 (IC50 = 3.7 μM) with anti-complementary, antioxidant and anticancer activity.

GNE-2256, also known as molecule 19, is an orally active compound that inhibits Interleukin 1 receptor-associated kinase 4 (IRAK4) with a K i of 1.4 nM and has an IL-6 inhibition concentration (IC50) of 190 nM.

Olcorolimus inhibits single allergen-induced allergic inflammation such as eosinophilic and lymphocytic infiltration and mRNA expression for interleukin (IL)-4 and IL-5

MMK1 TFA is a potent, selective agonist for the human formyl peptide receptor like-1 (FPRL-1/FPR2), exhibiting EC50 values of <2 nM for FPRL-1 and >10,000 nM for FPR1. This compound acts as a powerful chemotactic and calcium-mobilizing agent, effectively activating phagocytic leukocytes. It significantly enhances the Pertussis Toxin-sensitive production of proinflammatory cytokines IL-1b and IL-6 by human monocytes. Additionally, MMK1 TFA has been demonstrated to exhibit anxiolytic-like activity [1] [2] [3] [4].

YM-341619 (AS1617612) is a potent, orally active STAT6 inhibitor (IC50: 0.70 nM). YM-341619 inhibits IL-4-induced Th2 differentiation in mouse splenic T cells with an IC50 value of 0.28 nM, but does not affect Th1 cell differentiation. YM-341619 is a compound with potential for use in the study of allergic diseases, such as allergic asthma.

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

4-Maleimidosalicylic acid is a polar maleimide compound that does not exhibit suppressive effects on IL-2 production in JURKAT T cells.

2-heptyl-3-hydroxy-4(1H)-Quinolone (Pseudomonas Quinolone Signal) is a quorum-sensing signalling molecule produced by Pseudomonas aeruginosa in response to increased cell density. It increases the expression of the lasB gene in P. aeruginosa, the secretion of the metabolites pyocyanin and the lectin PA-IL, as well as increasing biofilm production in P. aeruginosa populations. It also reduces the iron content of the P. aeruginosa growth medium when used at a concentration of 40 μM and acts as an iron chelator in iron sulphate solutions.

GS143 is a selec­tive IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 sup­presses NF-κB acti­va­tion and tran­scrip­tion of tar­get genes and does not inhibit proteasome activity. GS143 has anti-asthm

JC-171, a selective inhibitor of the NLRP3 inflammasome, effectively inhibits LPS/ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8.45 μM[1].