Ironing Out the Mechanism of gp130 Signaling

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Essam Eldin A. Osman, Nouri Neamati, Des Richardson
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引用次数: 0

Abstract

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.

Abstract Image

厘清 gp130 信号传递机制
gp130 不仅是白细胞介素(IL)-6 的共享信号转导亚基,也是其他八种人类细胞因子受体复合物的共享信号转导亚基。通过 gp130 介导的 IL-6 信号转导途径包括经典、反式或集群信号转导,由影响 IL-6、其受体和 gp130 的各种调节剂错综复杂地调节。目前,已知的 gp130 小分子拮抗剂和激动剂数量有限。本综述旨在全面考察这些调节剂的现有知识,并深入了解它们的药理特性,尤其是在癌症和其他疾病方面。值得注意的是,本综述详细讨论了著名的 gp130 调节剂 SC144、bazedoxifene 和 raloxifene,并特别关注 SC144 的铁螯合特性。这为我们了解 SC144 的药理作用和在铁平衡非常重要的情况下的治疗潜力增添了新的维度。我们对 gp130 和铁平衡相关基因的生物信息学分析揭示了深刻的相关性,暗示了铁在 gp130 信号通路中的作用。总之,这篇综述有助于加深人们对 gp130 调节及其在各种疾病中的潜在治疗应用的理解。
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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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