Introduction: TANK-binding kinase 1 (TBK1) is a noncanonical IκB kinase family member that regulates the innate immune response. Misregulation of TBK1 activity can promote inflammatory disorders and oncogenesis; therefore, TBK1 inhibitors are considered a promising therapy for inflammation and cancer.
Areas covered: In this review, the authors provide information on the role of TBK1 in human health and on recently developed inhibitors from patents granted from 2011 to 2014. The reader will gain an understanding of the mechanisms of TBK1 function as well as the structure and biological activity of recently developed TBK1 inhibitors. Google and NCBI search engines were used to find relevant patents and clinical information using "TBK1 inhibitor" as the search term.
Expert opinion: The role of TBK1 in various diseases has prompted the further investigation of significant targets. Although research on TBK1 inhibitors has increased over the last few years, only a few inhibitors of this kinase have been identified. In addition, almost all of the chemical inhibitors are modified from different scaffolds and/or chemotypes of pyrimidine. Specifically, compound BX795 is the representative one, which was first patented as a potent TBK1 inhibitor. Even though some compounds have displayed interesting potential inhibition and selectivity of TBK1 in vitro and in in vivo trials, the development of more efficient and selective TBK1 inhibitors is still required.
Keywords: BX795; TBK1 inhibitor; cancer therapy; inflammation; inhibitory selectivity; pyrimidine derivatives.