3ZW3

Fragment based discovery of a novel and selective PI3 Kinase inhibitor

Summary for 3ZW3

• Entry DOI: 10.2210/pdb3zw3/pdb
• Related: 1E8Y 1E8Z 1HE8 2A4Z 2A5U 2CHW 2CHX 2CHZ 2V4L 3ZVV
• Descriptor: PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT GAMMA ISOFORM, N-{6-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]imidazo[1,2-a]pyridin-2-yl}acetamide (3 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P48736
• Total number of polymer chains: 1
• Total formula weight: 111029.41

Authors

Brown, D.G.,Hughes, S.J.,Milan, D.S.,Kilty, I.C.,Lewthwaite, R.A.,Mathias, J.P.,O'Reilly, M.A.,Pannifer, A.,Phelan, A.,Baldock, D.A. (deposition date: 2011-07-28, release date: 2011-09-28, Last modification date: 2024-05-08)

Primary citation

Hughes, S.J.,Millan, D.S.,Kilty, I.C.,Lewthwaite, R.A.,Mathias, J.P.,O'Reilly, M.A.,Pannifer, A.,Phelan, A.,Stuhmeier, F.,Baldock, D.A.,Brown, D.G.
Fragment based discovery of a novel and selective PI3 kinase inhibitor.
Bioorg. Med. Chem. Lett., 21:6586-6590, 2011

PubMed Abstract: We report the use of fragment screening and fragment based drug design to develop a PI3γ 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 PI3γ kinase inhibitor with good metabolic stability that was useful as a preclinical tool compound.

PubMed: 21925880
DOI: 10.1016/j.bmcl.2011.07.117

Experimental method

X-RAY DIFFRACTION (2.8 Å)