IL-1 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.

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.

PIPE-791 is an orally active, blood-brain barrier-permeable selective antagonist of LPAR1. PIPE-791 inhibits LPA-induced calcium mobilization, collagen expression, histamine release, and the activation of fibroblasts, microglia and macrophages. PIPE-791 induces oligodendrocyte precursor cell differentiation, myelination and remyelination, and increases the number of microglia in the retina of normotensive rats. PIPE-791 protects mature oligodendrocytes from cytokine-induced death, reduces the levels of pulmonary fibrosis markers and alleviates neuroinflammation in preclinical models. PIPE-791 can be used in the research of glaucoma, neuroinflammatory diseases, chronic osteoarthritis pain, idiopathic pulmonary fibrosis and multiple sclerosis.

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.

Inclisiran sodium is a double-stranded small interfering RNA (siRNA) molecule. Inclisiran sodium inhibits the transcription of PCSK9. Inclisiran sodium inhibits Pyroptosis, activates PPARγ, and reduces NLRP3, cleaved caspase-1, IL-1β, and IL-18. Inclisiran sodium has anti-inflammatory, lipid-regulating and anti-atherosclerotic activities. Inclisiran sodium can be used in researches of hyperlipidemia and cardiovascular disease (CVD).

Inclisiran is a double-stranded small interfering RNA (siRNA) molecule. Inclisiran inhibits the transcription of PCSK9. Inclisiran inhibits Pyroptosis, activates PPARγ, and reduces NLRP3, cleaved caspase-1, IL-1β, and IL-18. Inclisiran has anti-inflammatory, lipid-regulating and anti-atherosclerotic activities. Inclisiran can be used in researches of hyperlipidemia and cardiovascular disease (CVD).

IRF1-IN-1 (Compound I-2) is an IRF1 inhibitor. IRF1-IN-1 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-1 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1). IRF1-IN-1 has a protective effect on ionizing radiation-induced inflammatory skin injury.

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.

Neochlorogenic acid is a natural polyphenolic compound found in dried fruits and other plants. Neochlorogenic acid inhibits the production of TNF-α and IL-1β. Neochlorogenic acid suppresses iNOS and COX-2 protein expression. Neochlorogenic acid also inhibits phosphorylated NF-κB p65 and p38 MAPK activation.

Nidanilimab (CAN04) is a fully humanized monoclonal anti-IL1RAP antibody with a K_d value of 1.10 pM. Nidanilimab blocks IL1α and IL1β signaling and stimulates the immune system to destroy tumour cells. Nidanilimab can be used in research of non-small lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) .

Perfluorodecanoic acid (PFDA) is an orally active perfluoroalkyl substance. Perfluorodecanoic acid causes dysfunction of rat fetal Leydig cells via endoplasmic reticulum stress-mediated changes in lipid components. Perfluorodecanoic acid reduces testosterone biosynthesis in rat R2C Leydig cells by inducing endoplasmic reticulum stress. Perfluorodecanoic acid can be used in studies related to fetal Leydig cell dysfunction.

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.

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.

Periplogenin is an orally active cardiac glycoside found in Cortex periplocae. Periplogenin can induce ROS production and necroptosis and cause G0/G1 phase arrest. Periplogenin can inhibit pyroptosis by regulating the NLRP3/Caspase-1/GSDMD signaling. Periplogenin suppresses growth of prostate carcinoma cells by docking to an ATP1A1 protein pocket and forming a hydrogen bond with T804. Periplogenin can be used for the researches of cancer, inflammation and immunology, such as prostate carcinoma, rheumatoid arthritis and psoriasis.

Hyaluronic acid (Mw: 1000-2000 Da) is a long-chain unbranched polysaccharide with a molecular weight of 1000-2000 Da. Hyaluronic acid (Mw: 2000 Da) inhibits IL-1β expression and increases LC3-II. Hyaluronic acid (Mw: 1000-2000Da) can regulate tissue homeostasis and stress resistance, promote angiogenesis and tissue remodeling. Hyaluronic acid (Mw: 1000-2000 Da) has good biocompatibility and biodegradability, and can be used in drug delivery systems and tissue engineering. Hyaluronic acid (Mw: 2000 Da) can reduce facial skin blemishes and sagging.

LC-04-045 is a selective NIMA-related kinase 7 (NEK7) molecular glue degrader. LC-04-045 induces NEK7 degradation via the CRBN-based ubiquitin-proteasome system, dependent on the glycine 57-containing degron motif. LC-04-045 inhibits secretion of downstream cytokines IL-1β and IL-18. LC-04-045 can be used for the research of lymphoblastic leukemia.

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.