Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593455 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
Abstract
hSMG-1 kinase plays a dual role in a highly conserved RNA surveillance pathway termed nonsense-mediated RNA decay (NMD) and in cellular genotoxic stress response. Since deregulation of cellular responses to stress contributes to tumor growth and resistance to chemotherapy, hSMG-1 is a potential target for cancer treatment. From our screening efforts, we have identified pyrimidine derivatives as hSMG-1 kinase inhibitors. We report structure-based optimization of this pan-kinase scaffold to improve its biochemical profile and overall kinome selectivity, including mTOR and CDK, to generate the first reported selective hSMG-1 tool compound.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Ariamala Gopalsamy, Eric M. Bennett, Mengxiao Shi, Wei-Guo Zhang, Joel Bard, Ker Yu,