LASSBio, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Curr Drug Targets. 2018;19(16):1933-1942. doi: 10.2174/1389450119666180219120534.
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.
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.
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.
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.
核因子 κB（NF-κB）是一类转录因子家族，可促进许多基因的表达。NF-κB 生化级联的激活与先天和适应性免疫反应以及炎症等生理反应的调节有关。然而，NF-κB-IKKβ 途径的遗传异常和持续刺激与许多类型的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。
抑制 NF-κB-IKKβ 级联可以被认为是对抗这些慢性多因素疾病的新原型的有吸引力的治疗方法。
本文综述了一些作用于抑制 NF-κB-IKKβ 途径的原型和药物，突出了治疗应用的现实、挑战和前景。
尽管只有蛋白酶体抑制剂，如硼替佐米和卡非佐米，作为 NF-κB-IKKβ 途径中已知的可能靶点调节剂的治疗性有用药物是现实的，但一些被描述为 IKKβ 抑制剂的其他原型已进入临床试验阶段，作为控制炎症性疾病的候选药物。值得注意的是，一些在药物市场上可获得的经典药物，如乙酰水杨酸，最近也被描述为 IKKβ 抑制剂的 NF-κB 途径调节剂。
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