Human interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the discovery of IL-1β binders that interfere with IL-1β signaling. To this end, several technologies were used in parallel, including fragment-based screening (FBS), DNA-encoded library (DEL) technology, peptide discovery platform (PDP), and virtual screening. The utilization of distinct technologies resulted in the identification of new chemical entities exploiting three different sites on IL-1β, all of them also inhibiting the interaction with the IL-1R1 receptor. Moreover, we identified lysine 103 of IL-1β as a target residue suitable for the development of covalent, low-molecular-weight IL-1β antagonists.

中文翻译：

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通过综合命中鉴定方法评估 IL-1β 的配位性


人白介素-1β (IL-1β) 是一种促炎细胞因子，在调节免疫反应和各种炎症性疾病的发展中发挥着关键作用。在本出版物中，我们公开了我们在发现干扰 IL-1β 信号转导的 IL-1β 结合物方面所做的努力。为此，并行使用了多种技术，包括基于片段的筛选（FBS）、DNA编码库（DEL）技术、肽发现平台（PDP）和虚拟筛选。不同技术的利用导致了利用 IL-1β 上三个不同位点的新化学实体的鉴定，所有这些都还抑制与 IL-1R1 受体的相互作用。此外，我们确定了 IL-1β 的赖氨酸 103 作为适合开发共价低分子量 IL-1β 拮抗剂的目标残基。