NLRP3-IN-2

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.

NLRP3-IN-24 (Compound 15a) is an inhibitor targeting NLRP3, effectively suppressing the activation of the NLRP3 inflammasome.

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-20 is an effective oral inhibitor of NLRP3 inflammatory corpuscles, and the IC₅₀ secreted by IL-1β is 25nM. NLRP3-IN-20 showed good pharmacokinetic characteristics, and showed significant pharmacological activities in animal models such as nonalcoholic steatohepatitis, septic shock and colitis.

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].

NLRP3-IN-22 (Compound II-4) is an NLRP3 inhibitor with a 67% inhibition rate at 10 μM [1].

NLRP3-IN-25 (compound 32), an orally available NLRP3 inhibitor, exhibits anti-inflammatory properties by attenuating renal injury in a mouse model of doxorubicin-induced glomerulonephritis and inhibiting IL-1β secretion in THP-1 cells, with an IC 50 value of 21 nM [1].

NLRP3-IN-26 (compound 15Z), with an IC50 of 0.13 μM, functions as an inhibitor of NLRP3. It is applicable in studies involving the DSS-induced colitis model [1].

NLRP3-IN-27, a selective NLRP3 inhibitor with an IC50 of 0.55 μM, can be utilized in studies of inflammation and immunity [1].

NLRP3-IN-28 (compound N77) serves as a potent inhibitor of NLRP3, effectively blocking Nigericin-induced pyroptosis with an EC50 of 0.07μM. Additionally, it mitigates inflammatory reactions in vivo [1].

NLRP3-IN-29 (Compound 5M) is an inhibitor of NLR family pyrin domain containing 3 (NLRP3) with potential for blood-brain barrier permeability and inflammation inhibition both in vivo and in vitro. It can be used for research on Alzheimer's disease [1].

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].

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.

NLRP3-IN-64 (Compound 2) is an inhibitor of NLRP3, effectively suppressing its activation with an EC50 of 5 nM.

NEK7-IN-2 (compound 23) is a potent inhibitor of the NLRP3-NEK7 interaction. It enhances the thermal stability of NEK7 and modulates the assembly of the NLRP3 inflammasome. Additionally, NEK7-IN-2 inhibits the release of IL-1β.

NLRP3-IN-69 (Compound 23) inhibits the activation of NF-κBp65 and the formation of the NLRP3 inflammasome. It suppresses the overexpression of IL-1β, iNOS, and COX-2 induced by LPS, and inhibits the production of NO (IC50=5.66 μM), thereby demonstrating anti-inflammatory activity.

NLRP3-IN-72 (Compound 2) is a benzimidazole derivative. It exhibits anti-inflammatory and antioxidant properties, with an IC50 of 0.3 μM for NLRP3 IL-1β, a PD50 of 0.4 μM for protection against cell pyroptosis, and an EC50 of 0.6 μM for inducing HO-1.

HNW005 is a dual inhibitor targeting the NLRP3 inflammasome and urate transporter 1 (URAT1). It exhibits an inhibition constant (KD) of 204.6 nM and an IC50 of 1.7 μM for NLRP3 inflammasome activation, while demonstrating an IC50 of 6.4 μM for inhibiting uric acid transmembrane transport. At an administered dose of 2 mg/kg in vivo, HNW005 achieves a uric acid reduction rate of 64.8%, effectively providing anti-inflammatory, analgesic, and urate-lowering effects by inhibiting NLRP3 inflammasome activation and uric acid transport. HNW005 is applicable for research in gouty arthritis.

COX-2/NLRP3-IN-1 (Compound 6k) is an inhibitor that targets COX-2 and NLRP3, exhibiting an IC50 value of 1.53 μM for COX-2. This compound exerts anti-inflammatory effects by inhibiting the NF-κB/NLRP3 signaling pathway.

NLRP3-IN-81 (N102) is an inhibitor capable of crossing the blood-brain barrier, effectively countering NLRP3 inflammasome-dependent pyroptosis with an EC50 of 0.029 μM for Nigericin-induced pyroptosis. It significantly suppresses caspase-1 activation and IL-1β release that depend on NLRP3. Additionally, NLRP3-IN-81 disrupts the interaction between NLRP3 and the adaptor protein ASC, while inhibiting ASC oligomerization. This compound is applicable in research on pyroptosis-related diseases, such as inflammatory bowel disease and type 2 diabetes.

CAII-IN-11 (Compound A1) is a dual-targeted compound that includes an hCA II inhibitor segment (IC₅₀= 2 nM) and a NO donor component. It also shows inhibitory activity against hCA IX, hCA XII, and hCA I, with IC₅₀ values of 6, 3, and 152 nM, respectively. CAII-IN-11 significantly elevates cGMP levels in human trabecular meshwork cells. Furthermore, it reduces apoptosis of retinal ganglion cells by decreasing oxidative stress (ROS levels), inhibiting astrocytes, and NLRP3 inflammasome activation. In a rabbit model, CAII-IN-11 demonstrates intraocular pressure-lowering activity, making it a potential candidate for glaucoma research.

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).

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].

NLRP3/AIM2-IN-2 is a novel potent inhibitor with different species-specific effects on NLRP3 and AIM2 inflammasome dependent pyroptosis with IC50 of 0.2392 ± 0.0233 μ M.