3zw3

FRAGMENT BASED DISCOVERY OF A NOVEL AND SELECTIVE PI3 KINASE INHIBITORFRAGMENT BASED DISCOVERY OF A NOVEL AND SELECTIVE PI3 KINASE INHIBITOR

Structural highlights 3zw3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 2chz, 2v4l, 2a4z, 1e8z, 3zvv, 1he8, 2chx, 2a5u, 1e8y, 2chw Activity: Phosphatidylinositol-4,5-bisphosphate 3-kinase, with EC number 2.7.1.153 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed We report the use of fragment screening and fragment based drug design to develop a PI3gamma kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed into potent and ligand efficient lead compounds using structure guided fragment growing and merging strategies. This led to a potent, selective, and cell permeable PI3gamma kinase inhibitor with good metabolic stability that was useful as a preclinical tool compound. Fragment based discovery of a novel and selective PI3 kinase inhibitor.,Hughes SJ, Millan DS, Kilty IC, Lewthwaite RA, Mathias JP, O'Reilly MA, Pannifer A, Phelan A, Stuhmeier F, Baldock DA, Brown DG Bioorg Med Chem Lett. 2011 Aug 6. PMID:21925880 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-Kinases

spinqualitylabelsall models 3zw3, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image