摘要
背景:核因子κB(NF-κB,NF-κB)是一类促进多种基因表达的转录因子。NF-κB生化级联的激活与天然免疫和适应性免疫反应及炎症等生理反应的调节有关。然而,NF-κB-IKKβ通路的遗传异常和持续刺激与多种炎症和自身免疫性疾病以及肿瘤细胞的发生和存活直接相关。目的:抑制NF-κB-IKKβ级联可被认为是一种治疗慢性多因素疾病新原型的有吸引力的治疗方法。结果:本文介绍了几种抑制NF-κB-IKKβ通路的原型机和药物,着重介绍了治疗应用的现实、挑战和前景。结论:虽然在NF-κB-IKKβ通路可能的靶点中,只有蛋白酶体抑制剂(如硼替佐米和卡夫唑米)是一种具有治疗作用的药物,但其他一些被描述为IKKβ抑制剂的原型已进入临床阶段,成为控制炎症性疾病的药物候选。值得注意的是,在医药市场上的一些经典药物,如乙酰水杨酸,最近也被描述为NF-κB通路调节剂作为IKKβ抑制剂。
关键词: NF-κB,IKKβ,炎症,癌症,蛋白酶体抑制剂,N-酰肼.
图形摘要
Current Drug Targets
Title:NF-κB-IKKβ Pathway as a Target for Drug Development: Realities, Challenges and Perspectives
Volume: 19 Issue: 16
关键词: NF-κB,IKKβ,炎症,癌症,蛋白酶体抑制剂,N-酰肼.
摘要: Background: Nuclear factor κB (NF-κB) comprises a family of proteins that act as transcription factors promoting the expression of many genes. Activation of NF-κB biochemical cascades is associated with the regulation of innate and adaptive immune responses and inflammation, among other physiological responses. However, genetic abnormalities and continuous stimulation of the NF- κB-IKKβ pathway are directly related to many types of inflammatory and autoimmune diseases, as well as to the genesis and survival of tumor cells.
Objectives: Inhibition of the NF-κB-IKKβ cascade can be considered an attractive therapeutic method for the genesis of new prototypes to combat these chronic multifactorial diseases.
Results: This review describes some prototypes and drugs that act to inhibit the NF-κB-IKKβ pathway, highlighting the realities, challenges and perspectives for therapeutic use.
Conclusion: Although only proteasome inhibitors, such as bortezomib and carfilzomib, are a reality as therapeutically useful drugs among the known modulators of possible targets in the NF-κB-IKKβ pathway, some other prototypes described as IKKβ inhibitors have entered clinical stages as drug candidates for the control of inflammatory diseases. It is important to note that some classical drugs available on the pharmaceutical market, such as acetylsalicylic acid, were also described more recently as NF-κB pathway modulators as IKKβ inhibitors.
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Cite this article as:
NF-κB-IKKβ Pathway as a Target for Drug Development: Realities, Challenges and Perspectives, Current Drug Targets 2018; 19 (16) . https://dx.doi.org/10.2174/1389450119666180219120534
DOI https://dx.doi.org/10.2174/1389450119666180219120534 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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