Abstract A33: Discovery of novel anti-cancer therapeutic agents for Notch activation complex kinase (NACK) targeting the Notch pathway

The Notch signaling pathway has been found to play an important role in multiple human cancers by regulating transcriptional programs. However, the mechanism by which Notch drives target gene transcription is still elusive. In our previous study, we have identified and characterized a novel Notch activation complex kinase, NACK, which acts as a Notch transcriptional co-activator and an essential regulator of Notch-mediated tumorigenesis and development. In this regard, NACK could become a putative drug target in anti-cancer therapies. The lack of three-dimensional (3D) structure of NACK hinders the designing of potential drug inhibitors. Therefore, computational methods are adopted to elucidate the structural and functional features of NACK, which further aid in designing new NACK inhibitors. Molecule docking (Glide) is utilized to obtain potential hit inhibitors for NACK, which will be validated using in-vitro and in-vivo assays. This will open avenues for the development of new therapies for Notch-dependent cancers. Citation Format: Xiaoxia Zhu, Zhiqiang Wang, Ke Jin, Luisana Astudillo, Wen Zhou, Jinshui Chen, Peter Buchwald, Stephan C. Schurer, Anthony J. Capobianco. Discovery of novel anti-cancer therapeutic agents for Notch activation complex kinase (NACK) targeting the Notch pathway. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A33.