4FUL

PI3 Kinase Gamma bound to a pyrmidine inhibitor

Summary for 4FUL

• Entry DOI: 10.2210/pdb4ful/pdb
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 4-({4-[3-(piperidin-1-ylcarbonyl)phenyl]pyrimidin-2-yl}amino)benzenesulfonamide (3 entities in total)
• Functional Keywords: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P48736
• Total number of polymer chains: 1
• Total formula weight: 111193.68

Authors

Gopalsamy, A.,Bennett, E.M.,Shi, M.,Zhang, W.G.,Bard, J.,Yu, K. (deposition date: 2012-06-28, release date: 2012-10-17, Last modification date: 2024-11-27)

Primary citation

Gopalsamy, A.,Bennett, E.M.,Shi, M.,Zhang, W.G.,Bard, J.,Yu, K.
Identification of pyrimidine derivatives as hSMG-1 inhibitors.
Bioorg.Med.Chem.Lett., 22:6636-6641, 2012

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.

PubMed: 23021994
DOI: 10.1016/j.bmcl.2012.08.107

Experimental method

X-RAY DIFFRACTION (2.47 Å)