1461658-67-2Relevant academic research and scientific papers
Potent and Selective CK2 Kinase Inhibitors with Effects on Wnt Pathway Signaling in Vivo
Dowling, James E.,Alimzhanov, Marat,Bao, Larry,Chuaqui, Claudio,Denz, Christopher R.,Jenkins, Emma,Larsen, Nicholas A.,Lyne, Paul D.,Pontz, Timothy,Ye, Qing,Holdgate, Geoff A.,Snow, Lindsay,O'Connell, Nichole,Ferguson, Andrew D.
, p. 300 - 305 (2016/03/22)
The Wnt pathway is an evolutionarily conserved and tightly regulated signaling network with important roles in embryonic development and adult tissue regeneration. Impaired Wnt pathway regulation, arising from mutations in Wnt signaling components, such as Axin, APC, and β-catenin, results in uncontrolled cell growth and triggers oncogenesis. To explore the reported link between CK2 kinase activity and Wnt pathway signaling, we sought to identify a potent, selective inhibitor of CK2 suitable for proof of concept studies in vivo. Starting from a pyrazolo[1,5-a]pyrimidine lead (2), we identified compound 7h, a potent CK2 inhibitor with picomolar affinity that is highly selectivity against other kinase family enzymes and inhibits Wnt pathway signaling (IC50 = 50 nM) in DLD-1 cells. In addition, compound 7h has physicochemical properties that are suitable for formulation as an intravenous solution, has demonstrated good pharmacokinetics in preclinical species, and exhibits a high level of activity as a monotherapy in HCT-116 and SW-620 xenografts.
3 -CYANO- 5 -ARYLAMINO-7 -CYCLOALKYLAMINOPYRROLO [1, 5 -A] PYRIMIDINE DERIVATIVES AND THEIR USE AS ANTITUMOR AGENTS
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, (2013/10/21)
The invention relates to chemical compounds of Formula (I): or a salt thereof. In some embodiments, the invention relates to inhibitors of CK2. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein and their use in the prevention and treatment of CK2-related conditions and diseases, e.g., cancer.
