Children's Cancer Therapy Development Institute, Beaverton, OR, 97005, USA.
Omics Data Automation, Beaverton, OR, 97005, USA.
Eur J Pharmacol. 2020 Apr 15;873:172981. doi: 10.1016/j.ejphar.2020.172981. Epub 2020 Jan 31.
Dysregulated activity of the transcription factors of the nuclear factor κb (NF-κB) family has been implicated in numerous cancer types, inflammatory diseases, autoimmune disease, and other disorders. As such, selective NF-κB pathway inhibition is an attractive target to researchers for preclinical and clinical drug development. A plethora of commercially and clinically available inhibitors claim to be NF-κB specific; however, such claims of specificity are rarely quantitative or benchmarked, making the biomedical literature difficult to contextualize. This imprecision is worsened because some NF-κB reporter systems have low signal-to-noise ratios. Herein, we use a robust, defined, commercially available reporter system to benchmark NF-κB agonists and antagonists for the field. We also functionally characterize a RELA fusion-positive ependymoma cell culture with validated NF-κB inhibitor compounds.
转录因子核因子 κB（NF-κB）家族的活性失调与多种癌症类型、炎症性疾病、自身免疫性疾病和其他疾病有关。因此，选择性 NF-κB 途径抑制是研究人员进行临床前和临床药物开发的一个有吸引力的目标。大量商业和临床可用的抑制剂声称是 NF-κB 特异性的；然而，这种特异性的说法很少是定量的或有基准的，这使得生物医学文献难以理解。这种不精确性因一些 NF-κB 报告系统的信噪比低而进一步恶化。在此，我们使用一种稳健、明确、商业可用的报告系统来为该领域的 NF-κB 激动剂和拮抗剂提供基准。我们还对 RELA 融合阳性室管膜瘤细胞培养物进行了功能表征，并使用经过验证的 NF-κB 抑制剂化合物进行了验证。
