1. Abstract 3907: Discovery and characterization of AZ285 as a potent and selective inhibitor of CK2 kinase
- Author
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Emma L. Cooke, Marat Alimzhanov, Christopher R. Denz, James E. Dowling, Larry Bao, Qing Ye, Zhong-Ying Liu, Paul Lyne, and Patrick Brassil
- Subjects
Cancer Research ,biology ,MAP kinase kinase kinase ,Kinase ,Wnt signaling pathway ,Serine ,Oncology ,Biochemistry ,Cancer research ,biology.protein ,PTEN ,Casein kinase 2 ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
Casein Kinase 2 (CK2) is a highly conserved and ubiquitously expressed serine/threonine kinase that regulates several key oncogenic signaling pathways, including PI3K/AKT, and NFkB and Wnt, and whose targeted overexpression in transgenic animal models results in neoplastic growth. Herein we describe the identification of AZ285, a potent pyrazolo[1,5-a]pyrimidine-derived inhibitor of CK2 with a high degree of kinase selectivity. AZ285 depletes levels of the CK2 substrates pAKTS129 and PTENS370 and induces apoptosis in cells in a concentration-dependent manner. Optimization of early leads was aided in part by cell wash-out experiments and X-ray cocrystallography with huCK2a and resulted in an agent with physical properties and DMPK characteristics suitable for evaluation in disease model studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3907. doi:1538-7445.AM2012-3907
- Published
- 2012