gp130 functions as a shared signal-transducing subunit not only for interleukin (IL)-6 but also for eight other human cytokine receptor complexes. The IL-6 signaling pathway mediated through gp130 encompasses classical, trans, or cluster signaling, intricately regulated by a diverse array of modulators affecting IL-6, its receptor, and gp130. Currently, only a limited number of small molecule antagonists and agonists for gp130 are known. This review aims to comprehensively examine the current knowledge of these modulators and provide insights into their pharmacological properties, particularly in the context of cancer and other diseases. Notably, the prominent gp130 modulators SC144, bazedoxifene, and raloxifene are discussed in detail, with a specific focus on the discovery of SC144’s iron-chelating properties. This adds a new dimension to the understanding of its pharmacological effects and therapeutic potential in conditions where iron homeostasis is significant. Our bioinformatic analysis of gp130 and genes related to iron homeostasis reveals insightful correlations, implicating the role of iron in the gp130 signaling pathway. Overall, this review contributes to the evolving understanding of gp130 modulation and its potential therapeutic applications in various disease contexts.

中文翻译：

---

消除 gp130 信号转导的机制


gp130 不仅作为白细胞介素 （IL）-6 的共享信号转导亚基发挥作用，还用于其他 8 种人细胞因子受体复合物。通过 gp130 介导的 IL-6 信号通路包括经典、反式或集群信号转导，受影响 IL-6、其受体和 gp130 的各种调节剂的复杂调节。目前，已知的 gp130 小分子拮抗剂和激动剂数量有限。本综述旨在全面检查这些调节剂的当前知识，并提供对其药理特性的见解，特别是在癌症和其他疾病的背景下。值得注意的是，详细讨论了突出的 gp130 调节剂 SC144、巴多昔芬和雷洛昔芬，特别关注 SC144 铁螯合特性的发现。这为理解其在铁稳态显着的情况下的药理作用和治疗潜力增加了一个新的维度。我们对 gp130 和铁稳态相关基因的生物信息学分析揭示了有见地的相关性，暗示了铁在 gp130 信号通路中的作用。总体而言，本综述有助于不断发展对 gp130 调节及其在各种疾病环境中的潜在治疗应用的理解。