Structural highlights
Publication Abstract from PubMed
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.
Identification of pyrimidine derivatives as hSMG-1 inhibitors.,Gopalsamy A, Bennett EM, Shi M, Zhang WG, Bard J, Yu K Bioorg Med Chem Lett. 2012 Nov 1;22(21):6636-41. doi: 10.1016/j.bmcl.2012.08.107., Epub 2012 Sep 7. PMID:23021994[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gopalsamy A, Bennett EM, Shi M, Zhang WG, Bard J, Yu K. Identification of pyrimidine derivatives as hSMG-1 inhibitors. Bioorg Med Chem Lett. 2012 Nov 1;22(21):6636-41. doi: 10.1016/j.bmcl.2012.08.107., Epub 2012 Sep 7. PMID:23021994 doi:http://dx.doi.org/10.1016/j.bmcl.2012.08.107
