NOD-like Receptor (NLR) Inhibitor

DPO-1 is a potent Kv1.5 and Kv1.3 (EC₅₀ = 3.1 μM) channels inhibitor with potential immunomodulatory and anti-inflammatory effects. DPO-1 reduces Kv1.3 current density, blunts Ca²⁺ influx in Ca²⁺-depleted Jurkat cells, and inhibits IL-2 secretion in activated Jurkat cells. DPO-1 inhibits Uric acid sodium (HY-B2130A) (MSU)-induced NLRP3 inflammasome activation by blocking Kv1.5-mediated K⁺ efflux. DPO-1 can be used for the study of immunologic disorders and atrial fibrillation.

Ergolide is an orally active dual inhibitor targeting NF-κB/p65 and NLRP3. Ergolide blocks the NF-κB signaling pathway and the nuclear translocation of p65, and irreversibly binds to the NACHT domain of NLRP3 to inhibit inflammasome assembly. Ergolide significantly reduces the production of inflammatory mediators (e.g., NO, PGE₂) and cytokines, induces cancer cell apoptosis, autophagy and ROS generation. Ergolide also enhances the anti-tumor effect of vincristine. Ergolide alleviates acute lung injury via an NLRP3-dependent mechanism, and effectively improves the survival rate and behavioral function of septic mice and inflammatory zebrafish models. Ergolide is used in the research of metastatic uveal melanoma, neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease), sepsis and acute lymphoblastic leukemia.

NLRP3-IN-80 (Compound 1) is an NLRP3 inhibitor that can be used for the study of inflammaging.

Moronic Acid is a triterpenoid compound, which is an orally available anti-HIV agent with anti-inflammatory activity. Moronic Acid can inhibit viral replication, with an EC₅₀ value of <1 μg/mL. Moronic Acid can be isolated from Brazilian propolis.

INF39 is an irreversible and noncytotoxic NLRP3 inhibitor.

Phoenixin-20 (PNX-20) is a neuropeptide that activates GPR173. Phoenixin-20 inhibits LPS-induced TLR-4/MyD88/NF-κB signaling, pro-inflammatory cytokines, adhesion molecules, MMPs, and cytotoxicity. Phoenixin-20 increases SIRT1 and inhibits NLRP3/ASC/caspase-1, oxidative stress, and IL-1β/IL-18. Phoenixin-20 alleviates ox-LDL-induced endothelial dysfunction, monocyte adhesion, adhesion molecules, cytokines, NADPH oxidase/NOX-4, and ROS. Phoenixin-20 promotes GPR173/STAT6-mediated anti-inflammatory polarization of microglia and neuroprotection. Phoenixin-20 can be used in research on dental pulp infection, pulmonary arterial hypertension, atherosclerosis, neuroinflammation, anxiety, and neurodegenerative diseases.

Daphnoretin (Dephnoretin; Thymelol) is a protein kinase C (PKC) activator that inhibits the expression of hepatitis B virus (HBV) surface antigen (HBsAg) and exhibits antiviral activity. Daphnoretin exerts its antitumor effects by inhibiting the activation of the PI3K/AKT signaling pathway and triggers the mitochondrial apoptosis pathway. Daphnoretin alleviates chondrocyte apoptosis and inflammatory responses by inhibiting endoplasmic reticulum stress and activation of the NLRP3 inflammasome. Daphnoretin regulates the differentiation and maturation of dendritic cells, inhibits their immunostimulatory function by downregulating the phosphorylation level of JNK, and thus exerts a protective effect in skin graft rejection.

NLRP3-IN-17 is a potent, selective and orally active NLRP3 inflammasome inhibitor with an IC₅₀ value of 7 nM. NLRP3-IN-17 significantly inhibits NLRP3 dependent IL-1β secretion in mice and can be used for chronic inflammatory diseases research.

Suciraslimab (SM03) is an anti-human CD22 monoclonal antibody. Suciraslimab inhibits NLRP3 and ASC signaling. Suciraslimab suppresses cytokine (IL-1β, IL-12, IL-23) secretion and α4 integrin expression. Suciraslimab improves working memory and neuroinflammation. Suciraslimab isotype control product: Human IgG1 kappa, Isotype Control (HY-P99001).

Magnesium isoglycyrrhizinate hydrate (18α-Glycyrrhizic acid Magnesium hydrate; 18α-GA Magnesium hydrate; 18α-Licorice-saponin H2 Magnesium hydrate) is a derivative of glycyrrhizic acid with oral activity. Magnesium isoglycyrrhizinate hydrate exhibits antioxidant, anti-inflammatory, hepatoprotective and cardioprotective activities. Magnesium isoglycyrrhizinate hydrate protects against ethanol-induced alcoholic liver disease in rats by upregulating the expression levels of SOD, GSH, PPAR-α and CPT-1. Magnesium isoglycyrrhizinate hydrate shows cytotoxicity against T lymphocytes and inhibits HIV-1 replication in these cells. Magnesium isoglycyrrhizinate hydrate alleviates oxidative stress by reducing the levels of ROS, Nrf2, HO-1 and p-P65, and alleviates pyroptosis by downregulating the expression levels of NLRP3, GSDMD-N, P20 and c-IL-1β. Magnesium isoglycyrrhizinate hydrate inhibits autophagy, colonic fibrosis and myocardial fibrosis, and regulates intestinal barrier integrity. Magnesium isoglycyrrhizinate hydrate can be used in research related to alcoholic liver disease, HIV-1 infection, hepatotoxicity, acute liver failure, inflammatory bowel disease and myocardial fibrosis.

JC124 is a specific NLRP3 inflammasome inhibitor. JC124 has anti-inflammatory and neuroprotective effects.

SLC3037 is a NLRP3 inhibitor which blocks NLRP3 from binding to NEK7 or oligomerization, inhibiting inflammasome caused by MSU and other inflammasome activators. SLC3037 can be used for research of gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.

NT-0249 free base is an orally active NLRP3 inhibitor. NT-0249 has anti-inflammatory activity.

β-Aminoarteether (SM934 free base) is an Artemisinin derivative with orally active. β-Aminoarteether can be used for inflammation and autoimmune disease research, such as lupus diseases.

Soyasaponin II is a saponin with antiviral activity. Soyasaponin II inhibits the replication of HSV-1, HCMV, influenza virus, and HIV-1. Soyasaponin II shows potent inhibition on HSV-1 replication. Soyasaponin II serves as a inhibitor for YB-1 phosphorylation and NLRP3 inflammasome priming and could protect mice against LPS/GalN induced acute liver failure.

Dexpramipexole ((R)-Pramipexole) is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Na_v1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more.

YQ128 is a potent and selective second-generation NLRP3 (NOD-like receptor P3) inflammasome inhibitor with an IC₅₀ of 0.30 μM. YQ128 significantly and selectively suppresses the production of IL-1β, but not TNF-α, and it can cross the BBB to reach the CNS. YQ128 has anti-inflammatory activity. YQ128 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

NP3-562 is an orally active NLRP3 Inhibitor. NP3-562 inhibits IL-1β release in the supernatant of Nigericin (HY-127019)-stimulated THP-1 cells (IC₅₀ = 66 nM), human whole blood (IC₅₀ = 214 nM) and a mouse acute peritonitis model. NP3-562 can be used for the study of acute peritonitis.

Nigakinone is an orally active FXR agonist and NLRP3 inhibitor. Nigakinone suppresses bile acid-induced inflammation and cell damage, regulates the bile acid profile, and alleviates intestinal mucosal barrier injury. Nigakinone synergizes with Irinotecan (HY-16562) to inhibit the proliferation and migration of colorectal cancer cells as well as the growth of subcutaneous xenograft tumors. Nigakinone can be used in research related to ulcerative colitis and colorectal cancer.

Neral is a plant-derived anti-inflammatory, antioxidant and anticancer agent. Neral inhibits the phosphorylation of ERK1/2, p38 MAPK and IκB in macrophages induced by LPS (HY-D1056), suppresses the secretion of TNF-α and IL-6, as well as the expression of pro-IL-1β, iNOS and COX-2 in cells, and reduces the production of ROS in cells. Neral inhibits the activation of the NLRP3 inflammasome, and decreases the activation of caspase-1 and the secretion of IL-1β in mouse macrophages. Neral induces autophagy, and exhibits antiproliferative activity both in in vitro breast cancer cell models and mouse xenograft models. Neral regulates brassinosteroid, jasmonic acid and ethylene signaling pathways, and induces the expression of AP2/ERF-ERF and bHLH family genes in rice roots. Neral acts as a herbicide safener, alleviates the damage induced by Fenoxaprop-P-ethyl (HY-B2013), and promotes the elongation of rice roots. Neral can be used in research related to breast cancer, inflammatory and immune system diseases, and herbicide safeners.