Interleukin Related Inhibitor

Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1), used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Disulfiram, a copper ion carrier, with Cu²⁺ increases intracellular ROS levels and induces cuproptosis.

Resatorvid (TAK-242) is a selective Toll-like receptor 4 (TLR4) inhibitor. Resatorvid inhibits NO, TNF-α and IL-6 production with IC_50s of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy and plays pivotal role in various inflammatory diseases.

iST2-1 is an Stimulation-2 (ST2) inhibitor with an IC₅₀ value of 46.65 μM, blocks interaction between ST2 and IL-33, inhibits downstream signaling. iST2-1 functions as an immunomodulator, reduces proliferation of CD4⁺ and CD8⁺ T cells, increases regulatory T cell populations, reduces IFN-γ⁺CD4⁺ T cell populations, increases Foxp3⁺CD4⁺ regulatory T cell populations in the gastrointestinal tract. iST2-1 reduces plasma soluble ST2 and IFN-γ levels, reduces graft-versus-host disease scores, improves survival in graft-versus-host disease animal models, preserves graft-versus-tumor effect. iST2-1 can be used for the research of graft-versus-host disease.

TSLP-IN-1 is a potent thymic stromal lymphopoietin (TSLP) inhibitor. TSLP-IN-1 disrupts TSLP-TSLPR protein-protein interaction, and downregulates IL-4 and IL-13. TSLP-IN-1 can be used for the research of inflammation diseases, such as skin disease, asthma, and allergies.

Dupilumab (REGN-668) is a fully human mAb to IL-4 receptor α (IL-4Rα) that inhibits both IL-4 and IL-13 signaling, markedly improved moderate-to-severe atopic dermatitis.

Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.

Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC₅₀ of 0.2 nM and a K_i of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus.

GY4137 is a sustained-release H2S donor possessing vasodilatory, antihypertensive, and anti-inflammatory activities. GY4137 can inhibit cell growth, induce apoptosis, and cause cell cycle arrest by blocking the STAT3 pathway, demonstrating potent anticancer activity.

Beta-Sitosterol (purity>98%) is orally active. Beta-Sitosterol exhibits multiple activities, including anti-inflammatory, anticancer, antioxidant, antimicrobial, antidiabetic, antioxidant enzyme, and analgesic. Beta-Sitosterol inhibits inflammation and impaired adipogenesis in bovine mammary epithelial cells by reducing levels of ROS, TNF-α, IL-1β, and NF-κB p65 and restoring the activity of the HIF-1α/mTOR signaling pathway. Beta-Sitosterol induces apoptosis in cancer cells through ROS-mediated mitochondrial dysregulation and p53 activation. Beta-Sitosterol exerts its anticancer effects in cancer cells by activating caspase-3, caspase-8, and caspase-9, mediating PARP inactivation, MMP loss, altered Bcl-2-Bax ratio, and cytochrome c release. Beta-Sitosterol modulates macrophage polarization and reduces rheumatoid inflammation in mice. Beta-Sitosterol inhibits tumor growth in multiple mouse cancer models. Beta-Sitosterol can be used in the research of arthritis, lung cancer, breast cancer and other cancers, diabetes, etc.

Apilimod (STA 5326) is a potent IL-12/IL-23 inhibitor, and strongly inhibits IL-12 with IC₅₀s of 1 nM and 2 nM, in IFN-γ/SAC-stimulated human PBMCs and SAC-treated monkey PBMCs, respectively. Apilimod is a potent and highly selective PIKfyve inhibitor.

Sesame Oil is a vegetable oil. Sesame Oil can be extracted from the seeds of Sesamum indicum L. Sesame Oil decreases NF-κB, aspartate aminotransferase, alanine aminotransferase, IL-1β, IL-4 and nitric oxide. Sesame Oil has antitumor activity against malignant melanoma. Sesame Oil has protective effects against liver damage caused by various agents such as Cisplatin (HY-17394) and Acetaminophen (HY-66005). Sesame Oil shows antinociceptive and anti-inflammatory activities.

Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC₅₀=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC₅₀ >10 μ M). Ritlecitinib rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).

Ustekinumab is an anti-IL-12/IL-23 IgG1κ human monoclonal antibody.

Secukinumab (AIN457) is a high affinity, human monoclonal antibody targeted against interleukin (IL)-17A. Secukinumab is the first-in-class anti-IL-17 agent used for the research of plaque psoriasis, ankylosing spondylitis and psoriatic arthritis.

Omalizumab is a recombinant, humanized, monoclonal antibody against human immunoglobulin E (IgE) with a K_D of 0.393 nM. Omalizumab binds to the human FcγRIIb receptors with a K_D of 6.37 uM. Omalizumab has the potential for persistent allergic asthma research. The component ratio of this product is Active ingredient : Excipients = 1:1.3-1:1.5.

Risankizumab (BI 655066) is a humanised IgG monoclonal antibody, targeting IL-23 p19 subunit (K_d <10 pM) and inhibiting IL-17 production induced by human IL-23 in mouse splenocytes (IC₅₀ = 2 pM). Risankizumab can be used to research immunological and inflammatory disorders such as psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis and erythrodermic psoriasis.

Lebrikizumab (TNX-650) is an IgG4 humanized anti-interleukin-13 (IL-13) mAb with anti-itch effects that specifically binds to IL-13 in a non-receptor binding domain and inhibits its function. Lebrikizumab inhibits the IL-13 driven Th2 inflammatory response and blocks the signaling of IL-4Rα/IL-13Rα1. Lebrikizumab can be used for the research of asthma, atopic dermatitis and neuroinflammatory diseases.

IKK 16 is an orally active IKK inhibitor. IKK 16 shows IC₅₀s of 40 nM, 70 nM, 200 nM, and 50 nM for IKK2, IKK complex, IKK1, and LRRK 2, respectively. IKK 16 is also a pan-PKD inhibitor, inhibiting PKD1, PKD2, and PKD3 with IC₅₀s of 153.9, 115, and 99.7 nM, respectively. IKK 16 is also an ABCB1 inhibitor, interfering with the binding of ABCB1 to its substrates. IKK 16 protects against LPS (HY-D1056)-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure. IKK 16 can restore renal function and alleviate fibrosis in acute kidney injury. IKK 16 attenuates cardiac dysfunction associated with polymicrobial sepsis in mice with type 2 diabetes mellitus (T2DM) by inhibiting the NF-κB pathway.

Canakinumab (ACZ885) is a recombinant human anti-IL-1β monoclonal antibody. Canakinumab shows IC₅₀ values of 43.6 and 40.8 pM for human and marmoset IL-1β, respectively. The mode of action of canakinumab is based on the neutralization of IL-1β signaling, resulting in suppression of inflammation related to disorders of autoimmune origin.

Guselkumab is a recombinant human IgG1 monoclonal antibody against the IL-23p19 subunit. Guselkumab binds to human and cynomolgus monkey IL-23 with K_d values of 3.3 and 1.9 pmol/L, respectively. Guselkumab inhibits production of cytokines lying downstream of the IL-23 signaling pathway and can be used for psoriatic arthritis research.