NOD-like Receptor (NLR)

Isoliquiritigenin is a licorice chalconoid, a type of natural phenols that is currently under experimentation phase testing for use as a cancer treatment as well as an aide for cocaine addiction.

Mifamurtide is a liposomal formulation containing a muramyl dipeptide (MDP) analogue with potential immunomodulatory and antineoplastic activities

NOD-IN-1 is a potent mixed inhibitor of nucleotide-binding oligomerization domain (NOD)-like receptors, NOD1 and NOD2, with IC50 of 5.74 μM and 6.45 μM, respectively.

MCC950 sodium is a potent NLRP3 inflammasome inhibitor that inhibits IL-1beta production with IC50 value of 7.5 nm.

Nodinitib-1 (ML130;CID-1088438) is a NOD1 inhibitor with an IC50 of 0.56 μM.

CY-09 is a NLRP3 inhibitor with Kd value of 500 nM. It directly binds to ATP-binding motif of NLRP3 NACHT domain.

INF39 is an irreversible and noncytotoxic NLRP3 inhibitor.

Nigericin sodium salt is an antibiotic from Streptomyces hygroscopicus that works by acting as an H+, K+, and Pb2+ ionophore, a NLRP3 activator.

Dapansutrile (OLT1177) is a potent, selective and orally active inhibitor of NLRP3 inflammasome. Anti-inflammatory, analgesic activity.

Arglabin is a sesquiterpene gamma-lactone is isolated from Artemisia glabella; anticancer natural compound.

MCC950 (CP-456773, CRID3) is a potent and selective inhibitor of NLRP3 (NOD-like receptor (NLR) family, pyrin domain-containing protein 3) with IC50 of 7.5 nM and 8.1 nM in BMDMs and HMDMs, respectively.

NVP-DFV890 (Compound 102) is a selective NLRP3 inhibitor that antagonizes NLRP3 inflammasome activity. It is a valuable tool for investigating therapeutic approaches in osteoarthritis research.

Nigericin is an antibiotic derived from Streptomyces hygroscopicus that act as a K+/H+ ionophore, promoting K+/H+ exchange across mitochondrial membranes. Nigericin is a NLRP3 activator. Nigericin shows promising anti-cancer activities through decreasing intracellular pH (pHi), and inactivation of Wnt/β-catenin signals. Nigericin induces pyroptosis through caspase 1/GSDMD in TNBC.

ATP (Adenosine 5'-triphosphate) is a central component of energy storage and metabolism in vivo. ATP provides the metabolic energy to drive metabolic pumps and serves as a coenzyme in cells. ATP is an important endogenous signaling molecule in immunity and inflammation. ATP can activate the NLRP3 inflammasome and induce IL-1β and chemokines secretion. ATP has anti-bacterial infection effects and can protect mice against bacterial infection in mice.

Muscone, a TNF receptor inhibitor, is derived from the traditional Chinese medicine musk. It effectively inhibits NF-κB signaling and NLRP3 inflammasome activation, resulting in a significant reduction of inflammatory cytokines such as IL-1β, TNF-α, and IL-6. This compound is valuable in research focused on inflammation, cardiac function restoration, and improving survival rates in various pathological conditions.

Aurantiamide is a selective antagonist of the Gastrin-Releasing Peptide Receptor (GRPR), demonstrating significant anti-inflammatory and neuroprotective properties. It effectively mitigates inflammation and oxidative stress in renal tissues by targeting GRPR-mediated pathways, including RIPK3/MLKL signaling and NF-κB activation, thereby providing protection against acute kidney injury and promoting endothelial function. Additionally, Aurantiamide inhibits M1 microglial polarization and NLRP3 activation, showcasing efficacy in improving outcomes in Alzheimer's disease mouse models. Its notable in vivo effectiveness extends to various acute kidney injury contexts, including ischemia/reperfusion, sepsis, and hypertension models.

Tabersonine hydrochloride is a selective NLRP3 inhibitor that targets the NACHT domain of the NLRP3 protein, effectively inhibiting its ATPase activity and oligomerization. This action prevents ASC spot formation and caspase-1 activation, leading to a reduction in pro-inflammatory cytokine release, including IL-1β. Additionally, Tabersonine hydrochloride inhibits K63-linked ubiquitination of TRAF6, interfering with NF-κB, PI3K/Akt, and p38 MAPK signaling pathways. Its applications extend to the study of NLRP3-driven inflammatory conditions, such as acute lung injury, sepsis, and peritonitis, as well as in liver cancer research, where it induces apoptosis through mitochondrial and death receptor pathways.

7-Oxogedunin is a potent inhibitor of pyroptosis, acting primarily on protein kinase R (PKR). It effectively protects macrophages from cell death induced by anthrax lethal toxin and inhibits the assembly of various inflammasomes, including NLRP1 and NLRP3, as well as the activation of caspase-1 through its effects on PKR. In addition to its role in cell survival, 7-Oxogedunin exhibits growth inhibitory activity against European corn borer larvae, making it valuable for research in LT toxicity and pest control.

NLRP3-IN-81 is a potent inhibitor targeting the NLRP3 inflammasome, effectively preventing NLRP3-dependent pyroptosis with an EC50 of 0.029 μM in cell models using Nigericin. This compound inhibits the activation of caspase-1 and the subsequent release of IL-1β by disrupting the interaction between NLRP3 and the adaptor protein ASC, thereby inhibiting ASC oligomerization. NLRP3-IN-81 is relevant for research into pyroptosis-related conditions, including inflammatory bowel diseases and type 2 diabetes.

NLRP3-IN-87 is a selective, orally active inhibitor of the NLRP3 inflammasome, exhibiting a Kd value of 0.23 μM. This compound directly targets the NACHT domain of NLRP3, effectively disrupting its interactions with NEK7 and ASC, thereby inhibiting ASC oligomerization and inflammasome assembly. NLRP3-IN-87 is known to suppress caspase-1 activation and IL-1β secretion, demonstrating significant anti-inflammatory and analgesic effects. It is particularly useful for investigating the pathophysiology of gout as it reduces joint swelling, inflammation, and pain in MSU-induced acute gout models.

NP3-146 sodium is a selective inhibitor of the NLRP3 inflammasome, effectively binding to the NACHT domain of NLRP3. This compound demonstrates significant inhibition of IL-1β release, achieving an IC50 value of 0.171 μM in LPS/Nigericin-stimulated bone marrow-derived macrophages (BMDM). NP3-146 sodium modulates the levels of cleaved Caspase-1 and cleaved IL-1β in cell supernatants, making it a valuable tool for research into inflammatory diseases.

Necrosulfonamide-d4 is a deuterium-labeled variant of Necrosulfonamide, a potent inhibitor of MLKL and Gasdermin D (GSDMD). This compound specifically targets the downstream oligomerization step of necroptosis and pyroptosis without affecting upstream signaling pathways. By attenuating the expression of pivotal kinases such as NLRP3 and caspase-1, Necrosulfonamide-d4 modulates inflammatory responses and activates the Nrf2 pathway, enhancing antioxidant enzyme activity. This reagent is valuable for research applications involving neurodegenerative diseases, inflammatory conditions, tissue damage, and programmed necrosis pathways.

NEK7 degrader-1 is a potent NEK7 degrader with a DC50 of 0.1 nM, specifically designed to modulate NF-kB signaling pathways. It effectively inhibits caspase-1 activity and reduces IL-1β release in macrophages upon NLRP3 inflammasome activation. This compound is applicable for research in autoinflammatory and autoimmune disorders, including multiple sclerosis, as well as neurodegenerative diseases like Alzheimer's disease, and metabolic disorders such as pericarditis and Type 2 diabetes.

GDC-2394 sodium is a selective NLRP3 inhibitor that exhibits potent activity against IL-1β, with IC50 values of 0.4 μM for human IL-1β and 0.1 μM for mouse IL-1β. This compound effectively inhibits NLRP3-induced caspase-1 activity while leaving NLRC4-dependent inflammasome activation unaffected. GDC-2394 sodium is particularly relevant for research into gouty arthritis and may serve as a valuable tool in the study of inflammatory diseases linked to NLRP3 activation.

NLRP3 Agonist 1 is a potent agonist targeting the NLRP3 inflammasome. This compound has been shown to activate Caspase-1, leading to the cleavage of pro-inflammatory cytokines pro-IL-1β and pro-IL-18 into their active forms. NLRP3 Agonist 1 can be utilized in research focused on inflammation and immune response pathways.

10-Hydroxydecanoic acid (10-HDAA) is a saturated fatty acid that possesses notable anti-inflammatory properties. It exhibits a range of biological activities including anti-malarial, anti-Leishmania, and insecticidal effects, while also enhancing antigen-specific immune responses. Mechanistically, 10-HDAA inhibits NF-κB activation and interferon regulatory factor 1 (IRF-1) translation, leading to reduced levels of interleukin 6 (IL-6) and nitric oxide (NO) in inflammatory cells. Additionally, it plays a role in mitigating neuroinflammatory responses through the p53-autophagy and p53-NLRP3 pathways, making it a valuable reagent for studies in immunology and inflammation research.

(+)–Magnoflorine chloride is an aporphine alkaloid that exhibits potent anti-inflammatory, anti-tumor, anti-fungal, and neuroprotective properties. This compound facilitates Parkin/PINK1-mediated mitochondrial autophagy and modulates the NLRP3/Caspase-1 pathway, demonstrating essential immunomodulatory effects. Additionally, it inhibits the JNK and TLR4/NF-κB signaling pathways while activating the Sirt1/AMPK pathway to reduce neuronal oxidative stress and apoptosis. The ability to regulate miR-410-3p and suppress HMGB1/NF-κB signaling further underscores its potential in therapeutic applications across various diseases.

NP3-146 is a potent inhibitor of the NLRP3 inflammasome, acting by locking the NACHT domain of NLRP3. It effectively reduces IL-1β release, with an IC50 value of 0.171 μM in LPS/Nigericin-stimulated bone marrow-derived macrophages (BMDM). Additionally, NP3-146 modulates the levels of cleaved Caspase-1 and cleaved IL-1β in cell supernatants, making it a valuable tool in the study of inflammatory diseases.

NLRP3 Modulator 8 is a selective modulator targeting the NLRP3 inflammasome, exhibiting a DC50 of 9 nM for NEK7 degradation. It effectively inhibits caspase-1 activity and IL-1β release in macrophages, demonstrating dose-dependent effects upon NLRP3 activation. This compound is valuable for research into autoinflammatory and autoimmune diseases, such as multiple sclerosis and Alzheimer's disease, as well as cardiovascular and metabolic disorders, including pericarditis and Type 2 diabetes.

GDC-2394 is a selective NLRP3 inhibitor that acts orally, demonstrating inhibitory effects on IL-1β with IC50 values of 0.4 μM for human IL-1β and 0.1 μM for mouse IL-1β. This compound effectively inhibits NLRP3-induced caspase-1 activity while sparing NLRC4-dependent inflammasome activation. GDC-2394 is valuable for research into inflammatory conditions such as gouty arthritis.

(E/Z)-Necrosulfonamide is a racemic compound that inhibits MLKL and Gasdermin D (GSDMD), targeting distinct programmed necrosis pathways, specifically necroptosis and pyroptosis. This compound impedes the oligomerization process of downstream executors without interfering with upstream signaling activation. It has been shown to reduce the expression of key kinases such as NLRP3 and caspase-1, activate the Nrf2 pathway, and downregulate various inflammatory factors. Research applications include studies related to neurodegenerative diseases, tissue damage, ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis, and hair loss.

(+)-Magnoflorine is an orally active aporphine alkaloid that serves as an anti-inflammatory, anti-tumor, anti-fungal, and neuroprotective agent. It promotes mitochondrial autophagy through Parkin/PINK1 mechanisms and inhibits the NLRP3/caspase-1 signaling pathway, demonstrating significant immunomodulatory effects. Additionally, (+)-Magnoflorine modulates JNK and TLR4/NF-κB pathways, activates Sirt1/AMPK, and alleviates oxidative stress and apoptosis in neuronal cells. Its capacity to upregulate miR-410-3p and inhibit the HMGB1/NF-κB pathway further supports its anti-tumor activity. Furthermore, (+)-Magnoflorine exhibits marked antifungal properties, making it a versatile reagent in chemical research.

1,2,4-Trimethoxybenzene is a selective inhibitor of the NLRP3 inflammasome, exerting its effects orally. It significantly suppresses NLRP3 activation induced by Nigericin or ATP, leading to reduced caspase-1 activation and IL-1β secretion. This compound specifically targets the NLRP3 inflammasome without influencing AIM2 inflammasome activation, and it prevents the oligomerization of ASC and the interaction between NLRP3 and ASC, thus inhibiting inflammasome assembly. 1,2,4-Trimethoxybenzene is valuable for researching autoimmune disorders such as experimental autoimmune encephalomyelitis, multiple sclerosis, and metabolic conditions like type 2 diabetes.

Tabersonine is a selective and orally active inhibitor of the NLRP3 inflammasome, targeting the NACHT domain to modulate its ATPase activity and prevent oligomerization. This mechanism effectively inhibits ASC speck formation and blocks caspase-1 activation, leading to reduced secretion of pro-inflammatory cytokines, including IL-1β. Additionally, Tabersonine interferes with K63-linked ubiquitination of TRAF6, disrupting NF-κB, PI3K/Akt, and p38 MAPK signaling pathways. It is primarily utilized in research on NLRP3-mediated inflammatory diseases, such as acute lung injury, sepsis, and peritonitis, as well as in studies related to liver cancer.

Inclisiran is a double-stranded small interfering RNA (siRNA) that specifically targets and inhibits the transcription of proprotein convertase subtilisin/kexin type 9 (PCSK9). By reducing PCSK9 levels, Inclisiran effectively modulates lipid metabolism and demonstrates anti-inflammatory properties, including the inhibition of pyroptosis and a decrease in NLRP3, cleaved caspase-1, IL-1β, and IL-18. This reagent is valuable for research applications focused on hyperlipidemia and cardiovascular diseases (CVD), as it supports studies aimed at understanding lipid regulation and atherosclerosis.

Homoeriodictyol is a flavanone metabolite of Eriocitrin that exhibits a range of biological activities. It enhances synaptic-related protein expression via NCOA4-mediated ferritin autophagy and offers potential cognitive benefits by improving memory impairment in mice through inhibition of the NLRP3 inflammasome. Additionally, Homoeriodictyol protects human endothelial cells against oxidative stress by activating the Nrf2 pathway and preventing mitochondrial dysfunction. Its anticancer properties are demonstrated through the inhibition of survival and migration in androgen-resistant prostate cancer cells, as well as its ability to induce apoptosis and enhance reactive oxygen species activity. Moreover, Homoeriodictyol displays antinociceptive effects in vivo.

Magnesium isoglycyrrhizinate hydrate is a potent NLRP3 inflammasome inhibitor derived from the licorice plant (Glycyrrhiza glabra). It displays significant anti-inflammatory properties, making it a valuable compound for research into inflammatory diseases. Its efficacy in attenuating conditions such as chronic obstructive pulmonary disease in preclinical rat models highlights its potential applications in respiratory research and therapeutic development.

Kirenol is a diterpenoid compound, an orally active apoptosis inducer and signaling pathway regulator, with a Kd value of 5.47 μM against the target CK2. Kirenol promotes the cleavage of Bid into tBid, regulates the protein levels/phosphorylation of Bax, Bcl-2, p53 and p21, and induces caspase-independent apoptosis, S-phase cell cycle arrest, ROS accumulation and cytotoxicity in cancer cells. Kirenol activates the CK2/AKT and AMPK-mTOR-ULK1 pathways, inhibits the signaling of NF-κB, TGF-β/Smads and NLRP3 inflammasome, and regulates the GSK3β, BMP and Wnt/β-catenin pathways. Kirenol induces autophagy, mitophagy and osteoblast differentiation, promotes mitochondrial fusion, and exerts antioxidant, anti-inflammatory, antifibrotic, renoprotective, cardioprotective, neuroprotective and analgesic effects. Kirenol is applicable to research related to chronic myeloid leukemia, ischemic stroke, diabetic nephropathy, heart failure, acute lung injury and osteoporosis.

Neral is a monoterpene compound that exhibits anti-inflammatory and anti-cancer properties. It functions by inhibiting pro-inflammatory cytokines such as TNF-α and IL-6, and it downregulates key inflammatory mediators including pro-IL-1β, iNOS, COX-2, and NLRP-3. Neral's biological activities make it valuable for research in inflammation and cancer treatment strategies.

Geranial, a derivative of geraniol, primarily targets inflammatory pathways. It exhibits anti-inflammatory activity by inhibiting the secretion of pro-inflammatory cytokines such as TNF-α and IL-6 from macrophages. Additionally, Geranial inhibits IL-1β secretion via the NLRP-3 inflammasome, making it a valuable tool for research focused on inflammation and immune response modulation.

gp91 ds-tat is a specific inhibitor of NADPH oxidase 2 (Nox2), effectively blocking the production of superoxide generated by this enzyme. This bioactive peptide has demonstrated the ability to reduce reactive oxygen species (ROS), lipid peroxidation, and iron levels induced by high glucose conditions. Additionally, gp91 ds-tat inhibits homocysteine-induced activation of NLRP3 inflammasomes and restores the activity of lysosomal TRPML1 channels. Research applications include studies on Alzheimer's disease, glomerular inflammation, and cardiovascular disease, with implications for improving cerebrovascular and cognitive functions in APP/PS1 mouse models.

Stavudine is an orally active nucleoside reverse transcriptase inhibitor (NRTI) that selectively targets HIV-1 and HIV-2. In addition to its antiviral properties, Stavudine inhibits mitochondrial DNA replication and has been shown to reduce NLRP3 inflammasome activation while modulating Amyloid-β autophagy. Furthermore, Stavudine is associated with the induction of apoptosis, making it a valuable tool for research in HIV treatment and cellular apoptosis mechanisms.

Sweroside, a potent Keap1/Nrf2 activator, is an iridoid glycoside that enhances Nrf2 nuclear translocation by competing with Keap1. This compound exhibits diverse biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects, while regulating lipid metabolism. Sweroside's ability to inhibit oxidative stress and NLRP3-mediated pyroptosis, alongside its activation of the SIRT1 and AMPK/mTOR pathways, makes it valuable for investigating conditions such as myocardial ischemia-reperfusion injury, leukemia, acute lung injury, and non-alcoholic fatty liver disease.

CYP51/PD-L1-IN-3 is a dual inhibitor targeting CYP51 and PD-L1, exhibiting potent antifungal activity with IC50 values of 0.205 μM and 0.039 μM, respectively. This compound induces early apoptosis in fungal cells by reducing levels of intracellular IL-2, NLRP3, and NF-κBp65 proteins. Additionally, CYP51/PD-L1-IN-3 causes mitochondrial damage and reactive oxygen species (ROS) accumulation, ultimately resulting in fungal lysis and cell death. This compound serves as a valuable tool for research in fungal infections and immune modulation.

CYP51/PD-L1-IN-2 is a quinazoline compound that functions as a dual inhibitor of CYP51 and PD-L1, exhibiting IC50 values of 0.263 μM and 0.017 μM, respectively. It displays notable antifungal activity by triggering early apoptosis in fungal cells, leading to significant reductions in intracellular IL-2, NLRP3, and NF-κBp65 protein levels. Additionally, CYP51/PD-L1-IN-2 induces mitochondrial damage and reactive oxygen species (ROS) accumulation, culminating in fungal lysis and subsequent cell death. This compound is valuable for research exploring antifungal mechanisms and cancer immunotherapy.

CYP51/PD-L1-IN-1 is a dual inhibitor targeting both CYP51 and PD-L1, exhibiting an IC50 of 0.884 μM for CYP51 and 0.083 μM for PD-L1. This quinazoline compound demonstrates notable antifungal activity by inducing early apoptosis in fungal cells while significantly reducing intracellular levels of IL-2, NLRP3, and NF-κBp65. Additionally, CYP51/PD-L1-IN-1 contributes to mitochondrial damage and reactive oxygen species (ROS) accumulation, ultimately leading to fungal lysis and cell death. This compound is valuable for research focused on antifungal therapies and immune modulation.

Candidalysin is a cytolytic peptide toxin derived from the pathogenic fungus Candida albicans, primarily targeting epithelial cells. This peptide is known for its ability to activate the EGFR-MAPK signaling pathway, which leads to increased expression of matrix metalloproteinases (MMPs) and calcium influx, as well as modulation of the c-Fos transcription factor through p38 MAPK and ERK1/2. Candidalysin plays a critical role in both mucosal and systemic infections by stimulating NLRP3 inflammasome activation, promoting inflammatory responses, neutrophil recruitment, and Th17 immunity. Additionally, it induces lactate dehydrogenase (LDH) release, resulting in membrane damage and cytotoxicity.

N4-Acetylcytidine is an RNA-modifying nucleoside metabolite produced during tRNA degradation, primarily via N-acetyltransferase 10 and additional enzymes. This compound has been shown to enhance NLRP3 inflammasome activation through the upregulation and release of HMGB1. N4-Acetylcytidine plays a crucial role in modifying the stability and translation efficiency of mRNA, tRNA, and rRNA, particularly in relation to enterovirus 71 RNA. Its applications extend to research in cancer, neuroinflammatory diseases, viral infections, and obesity.

Doxofylline is an orally active phosphodiesterase IV (PDE IV) inhibitor and adenosine A1 receptor (A1AR) antagonist. It exhibits anti-inflammatory properties by reducing mitochondrial reactive oxygen species (ROS) production and modulating various cellular pathways, including the NLRP3-TXNIP inflammasome activation. This compound is valuable for research related to respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and bronchospasm.

Carvedilol phosphate hemihydrate is a non-selective β/α-1 adrenergic receptor blocker. It demonstrates significant biological activity by inhibiting lipid peroxidation with an IC50 of 5 μM and acts as a multiple-action antihypertensive agent, with potential applications in treating angina and congestive heart failure. Additionally, carvedilol phosphate hemihydrate has been identified as an autophagy inducer that suppresses the NLRP3 inflammasome, making it valuable for research in inflammation and cardiovascular diseases.