inflammasome

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).

Carvedilol (SKF 105517) Phosphate is the phosphate salt form of carvedilol, a racemic mixture and adrenergic blocking agent with antihypertensive activity and devoid of intrinsic sympathomimetic activity. The S enantiomer of carvedilol nonselectively binds to and blocks beta-adrenergic receptors, thereby exerting negative inotropic and chronotropic effects, and leading to a reduction in cardiac output. In addition, both enantiomers of carvedilol bind to and block alpha 1-adrenergic receptors, thereby causing vasodilation and reducing peripheral vascular resistance.

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.

NLRP3 AIM2-IN-3 is a unique molecule that inhibits NLRP3 and AIM2 inflammasome activation in a species-specific manner. It has an IC50 value for cell lysis of 0.077 ± 0.008 μ M. NLRP3 AIM2-IN-3 is a potent inhibitor of NLRP3 and AIM2 inflammasome-dependent cell lysis with an IC50 value for cell lysis of 0.077 ± 0.008 μ M. NLRP3 AIM2-IN-3 inhibits LPS nigericin NLRP3 AIM2-IN-3 inhibits LPS nigericin-stimulated cell lysis in THP-1 macrophages with an IC50 value of 0.077 ± 0.008 μM. NLRP3 AIM2-IN-3 interferes with the interaction of NLRP3 or AIM2 with the bridging protein ASC, inhibiting oligomerization of ASC.

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.

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.

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.

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

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.

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.

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).

JC124 is an inhibitor of NLRP3 Inflammasome and exhibits neuroprotective and anti-inflammatory activities.

TNKS-2-IN-1 is a TNKS-2 inhibitor.TNKS-2-IN-1 inhibits TNKS-1 and TNKS-2 with IC50s of 259 nM and 1100 nM, respectively.TNKS-2-IN-1 has antimicrobial activity against E. coli and S. aureus.TNKS-2-IN-1 inhibits the release of IL-1β from the NLRP3 inflammasome (IC50: 5 μM) by inhibiting IL-1β release from ATP-stimulated J1A.774 cells.

hydrocotarnine is an inhibitor of Cbl.

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].

Oxidized low density lipoprotein (Human) (Human ox-LDL) plays a crucial role in atherogenesis and contributes to endothelial dysfunction through the cytoplasmic adapter protein TRAF3IP2. This compound also promotes endothelial cell activation, leads to increased production of adhesion molecules, and reduces eNOS activity and NO production. Additionally, Human ox-LDL activates the NLRP3 inflammasome in macrophages.

NLRP3-IN-49 (compound Z48) is a potent and specific inhibitor of NLRP3, displaying IC50 values of 0.26 μM in THP-1 cells and 0.21 μM in mouse bone marrow-derived macrophages. It directly binds to the NLRP3 protein with a dissociation constant (Kd) of 1.05 μM, effectively preventing the assembly and activation of the NLRP3 inflammasome, thereby exhibiting anti-inflammatory properties. NLRP3-IN-49 is utilized in the research of inflammatory bowel disease.

NLRP3-IN-46 (Compound 3k) activates the cholinergic anti-inflammatory pathway involved in neuro-immune modulation, thereby inhibiting the activation of the NLRP3 inflammasome. Furthermore, NLRP3-IN-46 suppresses the production of IL-1β in THP-1 cells induced by Uric acid sodium, making it relevant for research in gouty arthritis.