The NLRP3 inflammasome is an essential component of the innate immune system and has been implicated in neurodegenerative and inflammatory disorders. Therefore, there is increasing interest to develop inhibitors of the NLRP3 inflammasome to achieve disease intervention. Recently, we have developed a series of sulfonamide-based NLRP3 inhibitors as potential treatments for neurodegenerative diseases. One of the challenges for CNS therapeutics is blood-brain barrier penetration. Therefore, a method to detect and compare the blood-brain barrier penetration of these inhibitors is required but has not yet been established. In this study, we established a method to evaluate and quantify the blood-brain barrier penetration of JC-171, one of our lead NLRP3 inhibitors in comparison with MCC950, another known urea-based NLRP3 inhibitor using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method. The results suggest that this methodology has the ability to provide reliable measurements for brain exposure.

NLRP3 炎症小体是先天免疫系统的重要组成部分，与神经退行性疾病和炎症性疾病有关。因此，开发 NLRP3 炎症小体抑制剂以实现疾病干预的兴趣越来越大。最近，我们开发了一系列基于磺胺的 NLRP3 抑制剂作为神经退行性疾病的潜在治疗方法。CNS 疗法的挑战之一是血脑屏障渗透。因此，需要一种检测和比较这些抑制剂的血脑屏障渗透的方法，但尚未建立。在这项研究中，我们建立了一种方法来评估和量化 JC-171 的血脑屏障渗透，与 MCC950 相比，我们的主要 NLRP3 抑制剂之一，另一种已知的基于尿素的 NLRP3 抑制剂使用高效液相色谱串联质谱 (HPLC-MS/MS) 方法。结果表明，这种方法有能力为大脑暴露提供可靠的测量。