6AUD

PI3K-gamma K802T in complex with Cpd 8 10-((1-(tert-butyl)piperidin-4-yl)sulfinyl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Summary for 6AUD

• Entry DOI: 10.2210/pdb6aud/pdb
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 10-[(S)-(1-tert-butylpiperidin-4-yl)sulfinyl]-2-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine (3 entities in total)
• Functional Keywords: p110 delta, sbdd, transferase-transferase inhbitor complex, transferase/transferase inhbitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P48736
• Total number of polymer chains: 1
• Total formula weight: 111181.66

Authors

Murray, J.M.,Ultsch, M. (deposition date: 2017-08-31, release date: 2017-11-15, Last modification date: 2023-10-04)

Primary citation

Safina, B.S.,Elliott, R.L.,Forrest, A.K.,Heald, R.A.,Murray, J.M.,Nonomiya, J.,Pang, J.,Salphati, L.,Seward, E.M.,Staben, S.T.,Ultsch, M.,Wei, B.,Yang, W.,Sutherlin, D.P.
Design of Selective Benzoxazepin PI3K delta Inhibitors Through Control of Dihedral Angles.
ACS Med Chem Lett, 8:936-940, 2017

PubMed Abstract: A novel selective benzoxazepin inhibitor of PI3Kδ has been discovered. Beginning from compound , an αPI3K inhibitor, we utilized structure-based drug design and computational analysis of dihedral torsion angles to optimize for PI3Kδ isoform potency and isoform selectivity. Further medicinal chemistry optimization of the series led to the identification of , a highly potent and selective inhibitor of PI3Kδ.

PubMed: 28947940
DOI: 10.1021/acsmedchemlett.7b00170

Experimental method

X-RAY DIFFRACTION (2.015 Å)