1071129-72-0Relevant academic research and scientific papers
Identification of orally available naphthyridine protein kinase D inhibitors
Meredith, Erik L.,Ardayfio, Ophelia,Beattie, Kimberly,Dobler, Markus R.,Enyedy, Istvan,Gaul, Christoph,Hosagrahara, Vinayak,Jewell, Charles,Koch, Keith,Lee, Wendy,Lehmann, HansJoerg,Mckinsey, Timothy A.,Miranda, Karl,Pagratis, Nikos,Pancost, Margaret,Patnaik, Anup,Phan, Dillon,Plato, Craig,Qian, Ming,Rajaraman, Vasumathy,Rao, Chang,Rozhitskaya, Olga,Ruppen, Thomas,Shi, Jie,Siska, Sarah J.,Springer, Clayton,Van Eis, Maurice,Vega, Richard B.,Von Matt, Anette,Yang, Lihua,Yoon, Taeyoung,Zhang, Ji-Hu,Zhu, Na,Monovich, Lauren G.
experimental part, p. 5400 - 5421 (2010/11/18)
A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was proposed as a potential antihypertrophic mechanism with application as a heart failure therapy. As PKC was previously identified as the immediate upstream activator of PKD, PKD vs PKC selectivity was essential to understand the effect of PKD inhibition in models of cardiac hypertrophy and heart failure. The present study describes the modification of the HTS hit to a series of prototype pan-PKD inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds inhibited PKD activity in vitro, in cells, and in vivo following oral administration. Their effects on heart morphology and function are discussed herein.
[2, 6] NAPHTHYRIDINES USEFUL AS PROTEIN KINASE INHIBITORS
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, (2008/12/04)
The present invention provides a compound of formula I: (formula I) said compound is inhibitor of selective subset of kinases belonging to the AGC or calmodulin kinase family, such as for example MARK1/2/3, PKD-1/2/3, PKN-1/2, CDK-9, CaMKII, ROCK-I/II, inhibitors of histone deacetylase (HDAC) phosphorylation, or inhibitors of other kinases. Finally, the present invention also provides a pharmaceutical composition.
