IL-6 Inhibitor

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.

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.

THR-123 TFA is an orally active ALK3 peptide agonist. THR-123 TFA has a relatively weak binding to ALK2, but does not bind to ALK6. THR-123 TFA suppresses inflammation, Apoptosis and the epithelial-to-mesenchymal transition program and reverses established fibrosis in five mouse models of acute and chronic renal injury. THR-123 TFA can be used for the study of kidney fibrosis.

JTE-607, a highly selective inflammatory cytokine synthesis inhibitor, protects from endotoxin shock in mice. JTE-607 inhibits inflammatory cytokine production, including TNF-α, IL-1β, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC₅₀s of 11, 5.9, 8.8, 7.3 and 9.1 nM, respectively. Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) is the target of JTE-607.

LMT-28 is an orally active and the first synthetic IL-6 inhibitor that functions through direct binding to gp130. LMT-28 shows low toxicity and selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130.

Hydrocortisone hemisuccinate (Hydrocortisone 21-hemisuccinate), a glucocorticoid, is an orally active steroidal anti-inflammatory agent (SAID) with anti-inflammatory and immunomodulatory activities. Hydrocortisone hemisuccinate inhibits the bioactivity of IL-6 and IL-3 with IC₅₀ values of 6.7 and 21.4 μM, respectively. Hydrocortisone hemisuccinate can be used in the study of ulcerative colitis (UC) and recurrent oral ulcers.

SC144 is a first-in-class, orally active gp130 (IL6-beta) inhibitor. SC144 binds gp130, induces gp130 phosphorylation (S782) and deglycosylation, abrogates Stat3 phosphorylation and nuclear translocation, and further inhibits the expression of downstream target genes. SC144 shows potent inhibition of gp130 ligand-triggered signaling. SC144 induces apoptosis in human ovarian cancer cells.

Alvelestat (AZD9668) is an orally active, selective inhibitor of neutrophil elastase. Alvelestat reduces elastase activity, myeloperoxidase release, neutrophil recruitment and activation, and calcium phosphate precipitation; promotes smooth muscle cell colonization and collagen deposition; and inhibits the formation of neutrophil extracellular traps (NETs) as well as NET-derived neutrophil elastase activity. Alvelestat restores endothelial dysfunction, regulates antioxidant factors, improves the expression of endothelial tight junctions, reduces vascular leakage, and accelerates wound healing. Alvelestat prevents pulmonary hemorrhage, matrix protein degradation, airspace enlargement, and small airway wall remodeling; and alleviates cigarette-induced inflammatory responses. Alvelestat inhibits the growth of abdominal aortic aneurysms exacerbated by Porphyromonas gingivalis. Alvelestat can be used in research related to chronic obstructive pulmonary disease, abdominal aortic aneurysm, radiation-induced skin injury, and bronchiectasis.

VJDT is a TREM1 inhibitor that can effectively block TREM1 signaling. VJDT inhibits tumor cell proliferation and migration and induces cell cycle arrest. VJDT has immunomodulatory and antitumor activities, and can be used for the research of tumors such as melanoma.

Pyrrothiogatain is a transcription factor GATA3 inhibitor with an IC₅₀ of 54.7 μM. Pyrrothiogatain inhibits the DNA-binding activity of GATA3 and inhibits the T helper 2 (Th2) cell differentiation and expression of Th2 cytokines. Pyrrothiogatain shows anti-infection effect by inhibiting ACE2 expression. Pyrrothiogatain can be used for the researches of inflammation, immunology, infection and cancer, such as colon cancer and SARS-CoV-2 infection.

Bivalirudin, a hirudin analog and anticoagulant, is a direct thrombin inhibitor. Bivalirudin inhibits thrombin-mediated fibrinogen cleavage, coagulation factor activation, and platelet activation by reversibly binding to thrombin. In addition, Bivalirudin also has certain effects of anti-virus, anti-inflammation, and vascular endothelial barrier function protection. Bivalirudin can be used for the research of thrombotic diseases and others.

Guanosine 5'-diphosphate (GDP) sodium, 96% (HPLC) is a nucleoside diphosphate that activates adenosine 5'-triphosphate-sensitive K⁺ channel. Guanosine 5'-diphosphate sodium, 96% (HPLC) is an iron mobilizer, which forms a complex with hepcidin to inhibit the hepcidin-ferroportin (FPN) interaction and modulates the IL-6/stat-3 pathway. Guanosine 5'-diphosphate sodium, 96% (HPLC) ameliorates the Turpentine-induced anemia of inflammation (AI) in mice when combined with FeSO₄. Guanosine 5'-diphosphate sodium, 96% (HPLC) can be used in the research of AI.

Diallyl Trisulfide is an orally active anticancer agent that can be isolated from garlic. Diallyl Trisulfide has the ability to induce apoptosis and exhibits anticancer, anti-inflammatory, antioxidant, and antibacterial activities. Diallyl Trisulfide can be used to study a variety of cancers, including liver, colon and prostate cancer.

HS-276 is an orally active, potent and highly selective TAK1 inhibitor, with a K_i of 2.5 nM. HS-276 shows significant inhibition of TAK1, CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with IC₅₀ values of 8.25, 29, 33, 63, 125, 264, 270, 810, 1280, and 5585 nM, respectively. HS-276 reduces the expression of TNF, IL-6, and IL-1β. HS-276 can be used for rheumatoid arthritis (RA) research.

Muscone is the main active monomer of traditional Chinese medicine musk. Muscone inhibits NF-κB and NLRP3 inflammasome activation. Muscone remarkably decreases the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), and ultimately improves cardiac function and survival rate.

Ginsenoside Rh1 (Prosapogenin A2) inhibits the expression of PPAR-γ, TNF-α, IL-6, and IL-1β.

Anti-Mouse IL-6 Antibody (MP5-20F3) is an anti-mouse IL-6 IgG1 monoclonal antibody. Anti-Mouse IL-6 Antibody (MP5-20F3) reshapes the tumor microenvironment by blocking IL-6. Anti-Mouse IL-6 Antibody (MP5-20F3) can inhibit the STAT3 pathway and enhance T cell infiltration. Anti-Mouse IL-6 Antibody (MP5-20F3) can be used for researches on inflammation and infection conditions such as malignant pleural effusion (MPE).

Madecassic acid is isolated from Centella asiatica (Umbelliferae). Madecassic acid has anti-inflammatory properties caused by iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 inhibition via the downregulation of NF-κB activation in RAW 264.7 macrophage cells.

AF12198 is a potent, selective and specific peptide antagonist for human type I interleukin-1 receptor (IL1-R1) (IC₅₀=8 nM) but not the human type II receptor (IC₅₀=6.7 µM) or the murine type I receptor (IC₅₀>200 µM). AF12198 inhibits IL-1-induced IL-8 production (IC₅₀=25 nM) and IL-1-induced intercellular adhesion molecule-1 (ICAM-1) expression (IC₅₀=9 nM) in vitro. AF12198 has anti-inflammatory activities and blocks responses to IL-1 in vivo.

Forsythoside I is an orally active caffeoyl phenylethanoid glycoside (CPG) that can be isolated from Forsythia suspense (Thunb.) Vahl. Forsythoside I has anti-inflammatory activity and can exert a protective effect in a mouse model of acute lung injury.