Chronic unresolving inflammation is emerging as a key underlying pathological feature of many if not most diseases ranging from autoimmune conditions to cardiometabolic and neurological disorders. Dysregulated immune and inflammasome activation is thought to be the central driver of unresolving inflammation, which in some ways provides a unified theory of disease pathology and progression. Inflammasomes are a group of large cytosolic protein complexes that, in response to infection- or stress-associated stimuli, oligomerize and assemble to generate a platform for driving inflammation. This occurs through proteolytic activation of caspase-1-mediated inflammatory responses, including cleavage and secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and initiation of pyroptosis, an inflammatory form of cell death. Several inflammasomes have been characterized. The most well-studied is the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, so named because the NLRP3 protein in the complex, which is primarily present in immune and inflammatory cells following activation by inflammatory stimuli, belongs to the family of nucleotide-binding and oligomerization domain (Nod) receptor proteins. Several NLRP3 inflammasome inhibitors are in development, all with multi-indication activity. This review discusses the current status, known mechanisms of action, and disease-modifying therapeutic potential of RRx-001, a direct NLRP3 inflammasome inhibitor under investigation in several late-stage anticancer clinical trials, including a phase 3 trial for the treatment of third-line and beyond small cell lung cancer (SCLC), an indication with no treatment, in which RRx-001 is combined with reintroduced chemotherapy from the first line, carboplatin/cisplatin and etoposide (ClinicalTrials.gov Identifier: NCT03699956). Studies from multiple independent groups have now confirmed that RRx-001 is safe and well tolerated in humans. Additionally, emerging evidence in preclinical animal models suggests that RRx-001 could be effective in a wide range of diseases where immune and inflammasome activation drives disease pathology.

慢性未解决的炎症正在成为许多（如果不是大多数）疾病的关键潜在病理特征，从自身免疫性疾病到心脏代谢和神经系统疾病。失调的免疫和炎性体激活被认为是未解决炎症的主要驱动因素，这在某些方面提供了疾病病理学和进展的统一理论。炎性小体是一组大型胞质蛋白复合物，它们响应于感染或应激相关刺激，寡聚化并组装以产生驱动炎症的平台。这是通过蛋白水解激活 caspase-1 介导的炎症反应而发生的，包括促炎细胞因子白细胞介素 (IL)-1β 和 IL-18 的裂解和分泌，以及细胞焦亡（细胞死亡的一种炎症形式）的启动。已经表征了几种炎性体。研究最充分的是核苷酸结合域 (NOD) 样受体蛋白 3 (NLRP3) 炎性体，如此命名是因为复合物中的 NLRP3 蛋白在炎症刺激激活后主要存在于免疫和炎症细胞中，属于到核苷酸结合和寡聚化结构域 (Nod) 受体蛋白家族。几种 NLRP3 炎症小体抑制剂正在开发中，均具有多适应症活性。这篇综述讨论了 RRx-001 的现状、已知作用机制和疾病缓解治疗潜力，RRx-001 是一种直接 NLRP3 炎症小体抑制剂，正在几项晚期抗癌临床试验中进行研究，包括治疗第三阶段的 3 期试验线和超越小细胞肺癌 (SCLC)，一种无需治疗的适应症，其中 RRx-001 与重新引入的一线化疗、卡铂/顺铂和依托泊苷（ClinicalTrials.gov 标识符：NCT03699956）相结合。来自多个独立小组的研究现已证实 RRx-001 在人类中是安全且耐受性良好的。此外，临床前动物模型中出现的新证据表明，RRx-001 可能对免疫和炎性小体激活驱动疾病病理的多种疾病有效。