inflammasome

NLRP3-IN-2 (5-Chloro-N-(p-sulfamoylphenethyl)-o-anisamide), an intermediate capable of synthesizing glibenclamide, exerts an inhibitory effect on the formation of NLRP3 inflammatory vesicles in cardiomyocytes, limiting infarct size after myocardial ischemia/reperfusion in mice and has no effect on metabolism.

Nigericin sodium salt is an antibiotic, an NLRP3 activator, and a cationic ion carrier. Nigericin sodium triggers the activation of the NALP3 inflammasome, which inhibits Golgi function and suppresses the growth of Gram-positive bacteria.

Muscone (3-Methylcyclopentadecanone) is an organic compound that is the primary contributor to the odor of musk.

Adrenalone hydrochloride (Adrenalone HCl) is a dopamine β-oxidase inhibitor with a similar structure to the norepinephrine transporter (NET) ligand, with an IC50 of 36.9 μM. It is an adrenergic agonist that acts as a local vasoconstrictor and hemostatic agent.

ATP disodium salt (Adenosine-Triphosphate) is a P2 purinoceptor agonist.

Stavudine (BMY-27857), a nucleoside reverse transcriptase inhibitor analog of thymidine, has activity against HIV.

ATP disodium salt hydrate (Adenosine disodium triphosphate) is a nucleoside triphosphate used in cells as a coenzyme often called the molecular unit of currency of intracellular energy transfer.

ATP (Adenosine triphosphate) provides cellular energy, participates in overall energy balance, and maintains intracellular homeostasis. ATP can act as an extracellular signaling molecule through interactions with specific purinergic receptors to mediate a variety of processes including neurotransmission, inflammation, apoptosis, and bone remodeling.

BAY 11-7082 (BAY 11-7821) is an NF-κB inhibitor that suppresses TNFα-induced IκBα phosphorylation (IC50=10 μM) and also inhibits the ubiquitin-specific proteases USP7 and USP21 (IC50=0.19 0.96 μM).

Lobeglitazone Sulfate（CKD-501 Sulfate） is a novel thiazolidinedione with anti-inflammatory activity that inhibits LPS-induced NLRP3 inflammasome activation and hepatic inflammation, and can be used in the study of type 2 diabetes mellitus (T2DM).

INT-777 (S-EMCA) is a potent TGR5 agonist with an EC50 of 0.82 μM. INT-777 (S-EMCA) inhibits NLRP5-ASC inflammasome-mediated neuroinflammation via the TGR3 cAMP PKA signaling pathway after subarachnoid hemorrhage in rats.

NLRP3-IN-NBC6 is a potent, selective NLRP3 inflammasome inhibitor with an IC50 of 574 nM. It acts independently of Ca 2+ and inhibits Nigericin-induced inflammasome activation in THP-1 cells, as well as Imiquimod-induced IL-1β release from LPS-primed bone marrow-derived macrophages (BMDMs) [1].

NT-0796 is a brain-permeable, potent, and selective inhibitor of the inflammasome NLRP3, inhibiting NLRP3 activation.NT-0796 is a potential NDT-19795 delivery vector.

Dapansutrile is a potent, selective and orally active NLRP3 inflammasome inhibitor, with Anti-inflammatory and analgesic activity.

CP-456773 (MCC950 (CP-456773) and CRID3) is an effective and specific cytokine release inhibitor and NLRP3 inflammasome inhibitor. CP-456773 inhibits IL-1β secretion and caspase 1 processing. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced IL-1β production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

BC-1471 is a STAM-binding protein (STAMBP) deubiquitinase inhibitor that inhibits the inflammasome activity of NALP7 (NACHT, LRR, and PYD domains-containing protein 7) [1].

NLRP3-IN-9 (INF-4E) is an inhibitor of NLRP3 ATPase and caspase-1. NLRP3-IN-9 acts by irreversibly trapping thiol nucleophiles, which prevents both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner.

CP 424174 is an inhibitor of IL-1β post-translational processing with IC50 of 210 nM. Inhibits the formation of mature IL-1β. Indirectly inhibits NLRP3. Active in vivo and orally bioavailable.

YQ128 is a potent and selective second-generation NLRP3 (NOD-like receptor P3) inflammasome inhibitor with an IC50 of 0.30 µM and exhibits significant anti-inflammatory activity.

4'-Methoxyresveratrol (4'-O-Methylresveratrol) is a natural product from the roots of *Rheum palmatum* L., with significant hypoglycemic, anti-inflammatory, and antioxidant effects. 4'-Methoxyresveratrol alleviates AGE-induced inflammation by suppressing RAGE-mediated MAPK NF-κB signaling pathway and NLRP3 inflammasome activation.

hydrocotarnine is an inhibitor of Cbl.

Stavudine sodium (d4T), an orally active nucleoside reverse transcriptase inhibitor (NRTI), demonstrates activity against both HIV-1 and HIV-2. It also inhibits mitochondrial DNA (mtDNA) replication, reduces NLRP3 inflammasome activation, modulates Amyloid-β autophagy, and induces apoptosis [1] [2] [3] [4].

NLRP3-IN-21 (compound L38) is an inhibitor of the NLRP3 inflammasome with anti-inflammatory properties, suppressing inflammasome activation and pyroptosis by inhibiting gasdermin D cleavage, ASC oligomerization, and NLRP3 inflammasome assembly [1].

NLRP3-IN-4 is a highly efficient and orally bioavailable inhibitor of NLRP3 inflammasome, which exhibits strong anti-inflammatory properties specifically targeted towards colitis.

Isoandrographolide, a compound known for its cell differentiation-inducing and hepatoprotective effects, also inhibits NLRP3 inflammasome activation and mitigates silicosis in mice.

NLRP3-IN-16 is a potent, selective inhibitor of the NLRP3 inflammasome, effectively reducing IL-1β release with an IC50 of 0.065 μM, and is primarily utilized in inflammation research [1].

NLRP3-IN-17 is a potent, selective, and orally active inhibitor of the NLRP3 inflammasome with an IC50 of 7 nM, effectively inhibiting NLRP3-dependent IL-1β secretion in mice, making it valuable for chronic inflammatory disease research [1].

Azalamellarin N is a pyroptosis inhibitor that exhibits varying inhibitory effects on different pyroptosis inducers. It functions by targeting molecules upstream of NLRP3 inflammasome activation, instead of directly affecting the components of the NLRP3 inflammasome. Its inhibitory potency against various inducers is ranked as follows: Nigericin > R837 [1].

JT002 is an orally active NLRP3 inflammasome inhibitor that decreases the production of NLRP3-dependent proinflammatory cytokines (such as IL-1β, IL-1α, IL-18) and pyroptosis, as well as inhibits the formation of the NLRP3 inflammasome complex. Additionally, JT002 mitigates airway hyperresponsiveness and airway neutrophilia in mice [1].

GDC-2394, an orally active, selective NLRP3 inhibitor, also targets IL-1β, exhibiting inhibitory concentrations (IC50s) of 0.4 μM (human IL-1β) and 0.1 μM (mouse IL-1β). It effectively hampers NLRP3-induced caspase-1 activity while not affecting NLRC4-dependent inflammasome activation.

JT001 (NLRP3-IN-19) is a potent, specific, and orally active NLRP3 inhibitor that impedes the assembly of the NLRP3 inflammasome, suppressing cytokine release and preventing pyroptosis. JT001 is utilized in research on nonalcoholic steatohepatitis and liver fibrosis [1].

Emlenoflast sodium (MCC7840 sodium), a sulfonylurea, is a selective NLRP3 inflammasome inhibitor with an IC50 value of less than 100 nM for NLRP3 inflammasome, and can be used in the study of inflammatory diseases.

NLRP3-IN-10 (ZVN26391) is a potent NLRP3 inhibitor. NLRP3-IN-10 inhibits IL-1β release with an IC50 value of 251.1 nM. NLRP3-IN-10 attenuates ASC speck formation, leading to suppress activation of NLRP3 inflammasome.

ODN TTAGGG (A151) is an inhibitory oligonucleotide (ODN), a TLR9, AIM2 and cGAS antagonist. oDN TTAGGG competitively inhibits AIM2 inflammasome activation by DNA and inhibits cGAS activation, exhibiting immunosuppressive activity. ODN TTAGGG can be used to study autoimmune diseases such as lupus erythematosus. oDN TTAGGG sequence: 5'-T-T-A-G-G-G-T-T-A-G-G-G-G-T-T-A-G-G-G-G-G-T-T-A-G-G-G-G-G-G-3'.

Articaine (Hoe-045 free base), an amide anesthetic featuring an ester group, effectively relieves pain by reversibly binding to the α-subunit of the voltage-gated sodium channels located in the nerve's inner cavity. Furthermore, Articaine mitigates LPS-induced acute kidney injury through the suppression of NF-κB activation and inhibition of the NLRP3 inflammasome pathway.

NLRP3-IN-14 is a potent, selective inhibitor of the NLRP3 inflammasome, displaying a dissociation constant (K D) of 5.87 μM and an IC50 of 0.131 μM for inhibiting IL-1β release. It is applicable for inflammation research.

NLRP3-IN-15 is a potent, selective inhibitor of the NLRP3 inflammasome, demonstrating efficacy by inhibiting IL-1β (interleukin-1 beta) release with an IC50 value of 0.114 μM. This compound is utilized in the research of inflammation.

Hexokinase (ScHEX1), a glycolytic enzyme, is inhibited by n-acetylglucosamine, which causes it to detach from the mitochondrial outer membrane. This detachment activates the NLRP3 inflammasome [1].

JC-171, a selective inhibitor of the NLRP3 inflammasome, effectively inhibits LPS ATP-induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8.45 μM[1].

Emlenoflast (MCC7840) is a selective inhibitor of NLRP3 inflammasome.

Peptide5 TFA, a connexin 43 mimetic peptide, mitigates swelling, astrogliosis, and neuronal cell death in animal models of spinal cord injury, and suppresses the NLRP3 inflammasome, functioning as an anti-inflammatory agent (1) (2) (3).

QS-21, an immunostimulatory saponin, is a potent vaccine adjuvant that stimulates both Th2 humoral and Th1 cell-mediated immune responses by interacting with antigen presenting cells (APCs) and T cells. Furthermore, QS-21 activates the NLRP3 inflammasome, leading to the release of cytokines IL-1β and IL-18, dependent on caspase-1.

NDT-19795 is a potent NLRP3 inflammasome inhibitor with an IC 50 value of 66 nM using the PBMC method and 4.7 μM using the WB method. It is a carboxylic acid-active compound that can be derived from NT-0796 within cells, and is applicable for neurological disease research [1].

A 68930 is a dopamine D-1 receptor antagonist. A 68930 inhibits NLRP3 inflammasome activity.

Oxidized ATP trisodium salt (oATP) is a broad-spectrum P2 receptor inhibitor that irreversibly antagonizes P2X7R activation and inhibits CRP-induced NLRP3 inflammasome activation, making it useful in atherosclerosis research [1] [2].

Anti-inflammatory agent 50 (compound a1), a derivative of Fusidic acid, exerts its effects through inhibition of inflammatory mediators including NO, IL-6, and TNF-α. It mitigates acute lung injury by modulating these mediators and suppressing the MAPK, NF-κB, and NLRP3 inflammasome signaling pathways [1].

NLRP3-IN-23 (Compound 15C) is an inhibitor that significantly impedes heme-mediated activation of the NLRP3 inflammasome at a concentration of 0.1 μM [1].