gouty

Sulfinpyrazone (NSC-75925) is a uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties.

Colchicine is an orally active natural alkaloid that acts by inhibiting microtubule polymerization (IC50 = 3 nM) and as a competitive antagonist of the α3 glycine receptor. It possesses broad anti-inflammatory, immunosuppressive, and antifibrotic activities, can inhibit NLRP3 inflammasome activation to prevent NSAID-induced small intestine injury, holds potential for gouty arthritis and rheumatoid arthritis research, and is commonly used to establish Alzheimer’s disease models.

Uric acid sodium is a potent and widely recognized antioxidant with the ability to scavenge oxygen free radicals, helping to maintain blood pressure stability and counteract oxidative stress. It effectively eliminates reactive oxygen species (ROS), such as singlet oxygen and peroxynitrite, and inhibits lipid peroxidation. Additionally, uric acid sodium is closely associated with the pathogenesis of gouty arthritis and the formation of calcium oxalate stones, and it can be used to induce hypertension models.

Prudomestin (3,5,7-Trihydroxy-4',8-dimethoxyflavone) is a natural product isolated from the heartwood of Prunus domestica, with xanthine oxidase (XO) inhibitory activity with IC50 of 6 µM.

MPO-IN-8, an orally active myeloperoxidase (MPO) inhibitor, effectively inhibits the production of hypochlorous acid in neutrophils and the release of extracellular traps (NETosis). In mice exhibiting gouty arthritis, it reduces swelling, decreases peroxidase activity, and lowers IL-1β levels.

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.

NLRP3-IN-51 (Compound 3q) is an effective activator of the cholinergic anti-inflammatory pathway (CAP). This compound demonstrates potential for treating gouty arthritis as it inhibits the production of IL-1β in THP-1 cells induced by monosodium urate (MSU). Furthermore, NLRP3-IN-51 suppresses the phosphorylation of NF-κBp65 triggered by MSU without impacting the self-cleavage and activation of NLRP3, pro-caspase 1, or the second messenger caspase-1. Therefore, the initial stage of NLRP3 inhibition by NLRP3-IN-51 occurs through the activation of CAP.

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.

Sulindac (sodium) (MK-231) is an orally active nonsteroidal anti-inflammatory agent. Sulindac (sodium) is used to reduce pain, swelling, and joint stiffness from arthritis. Sulindac is also used for the research of arthritis of the spine, gouty arthritis. Sulindac (sodium), as an immunomodulatory agent, can downregulate PD-L1 through the blockade of NF-κB signaling and modulates the response of pMMR colorectal cancer (CRC) to anti-PD-L1 immunotherapy, inhibits the development and progression of colorectal cancer CRC. Sulindac (sodium) also inhibits TGF-β1- induced epithelial-mesenchymal transition (EMT) and suppresses lung cancer cell migration and invasion via downregulation of SIRT1 [1] [2].

P2Y14R antagonist 1 (compound I-17) is a selective and potent P2Y14R antagonist (IC50=0.6 nM) with oral activity and good bioavailability that inhibits monosodium urate-induced inflammatory response in acute gouty arthritis by reducing inflammatory factor release via the NLRP3/GSDMD signaling pathway and cellular pyroptosis.