Download MendeleyIdentification of pyrimidine derivatives as hSMG-1 inhibitors.
Gopalsamy, A., Bennett, E.M., Shi, M., Zhang, W.G., Bard, J., Yu, K.(2012) Bioorg Med Chem Lett 22: 6636-6641
- PubMed: 23021994
- DOI: https://doi.org/10.1016/j.bmcl.2012.08.107
- Primary Citation of Related Structures:
4FUL - PubMed 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.
Organizational Affiliation:
Worldwide Medicinal Chemistry, Pfizer, 200 Cambridgepark Drive, Cambridge, MA 02140, USA. ariamala.gopalsamy@pfizer.com
