Dapansutrile is an oral, small-molecule, selective NLRP3 inflammasome inhibitor [1]. Dapansutrile blocks the assembly and activation of NLRP3, Dapansutrile inhibits downstream caspase-1 activation and the maturation and release of IL-1β and IL-18, alleviating the inflammatory response [2-3]. Dapansutrile is primarily used to treat gouty arthritis [4].
In chondrocytes, Low-dose Dapansutrile (0-10μM; 24h) had no significant cytotoxicity to rat chondrocytes [5]. In BV2 cells, Dapansutrile (100μM; 24h) inhibits cell proliferation [6].
In db/db mouse model, Dapansutrile (200mg/kg; ip; 8 weeks) treatment can alleviate dyslipidemia and hepatic lipid metabolism and function [7]. In acute myocardial infarction mouse model, Dapansutrile (6-600mg/kg; ip; single injection) treatment reduced infarct size in a dose-dependent manner [8].
References:
[1]. Sánchez-Fernández A, Skouras D B, Dinarello C A, et al. OLT1177 (Dapansutrile), a selective NLRP3 inflammasome inhibitor, ameliorates experimental autoimmune encephalomyelitis pathogenesis[J]. Frontiers in immunology, 2019, 10: 2578.
[2]. Toldo S, Mauro A G, Cutter Z, et al. The NLRP3 inflammasome inhibitor, OLT1177 (dapansutrile), reduces infarct size and preserves contractile function after ischemia reperfusion injury in the mouse[J]. Journal of Cardiovascular Pharmacology, 2019, 73(4): 215-222.
[3]. Elsayed M S, Abu-Elsaad N M, Nader M A. The NLRP3 inhibitor dapansutrile attenuates folic acid induced nephrotoxicity via inhibiting inflammasome/caspase-1/IL axis and regulating autophagy/proliferation[J]. Life sciences, 2021, 285: 119974.
[4]. Klück V, Tim L, Janssen M, et al. Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial[J]. The Lancet Rheumatology, 2020, 2(5): e270-e280.
[5]. Tang L, Sim I, Moqbel S A A, et al. Dapansutrile ameliorated chondrocyte inflammation and osteoarthritis through suppression of MAPK signaling pathway[J]. Human & Experimental Toxicology, 2022, 41: 09603271221145401.
[6]. Wu P, Tang X, Cui K, et al. OLT1177 (Dapansutrile) Attenuates Retinal Neovascularization by Inhibiting NLRP3 Inflammasome Activation[J]. Investigative Ophthalmology & Visual Science, 2022, 63(7): 1759–F0219-1759–F0219.
[7]. Wu Y, Zhou J. Dapansutrile Regulates Mitochondrial Oxidative Stress and Reduces Hepatic Lipid Accumulation in Diabetic Mice[J]. Current Issues in Molecular Biology, 2025, 47(3): 148.
[8]. Toldo S, Mauro A G, Cutter Z, et al. The NLRP3 inflammasome inhibitor, OLT1177 (dapansutrile), reduces infarct size and preserves contractile function after ischemia reperfusion injury in the mouse[J]. Journal of Cardiovascular Pharmacology, 2019, 73(4): 215-222.
Dapansutrile是一种口服小分子选择性NLRP3炎症小体抑制剂 [1]。Dapansutrile阻断NLRP3的组装和激活，抑制下游caspase-1的活化以及IL-1β和IL-18的成熟和释放，从而减轻炎症反应 [2-3]。Dapansutrile主要用于治疗痛风性关节炎 [4]。
在软骨细胞中，低剂量Dapansutrile（0-10μM；24h）对大鼠软骨细胞无显著细胞毒性 [5]。在BV2细胞中，Dapansutrile（100μM；24h）可抑制细胞增殖 [6]。
在db/db小鼠模型中，Dapansutrile（200mg/kg；ip；8周）治疗可改善血脂异常、肝脏脂质代谢和功能 [7]。在急性心肌梗死小鼠模型中，Dapansutrile（6-600mg/kg；ip；单次注射）治疗以剂量依赖性方式减少梗死面积 [8]。