4g11 | pdb_00004g11

X-ray structure of PI3K-gamma bound to a 4-(morpholin-4-yl)- (6-oxo-1,6-dihydropyrimidin-2-yl)amide inhibitor

spinqualitylabelsall models 4g11, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g11 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: 0W7 Gene: PIK3CG (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed From a HTS campaign, a new series of pyrimidone anilides exemplified by compound 1 has been identified with good inhibitory activity for the PI3Kbeta isoform. The structure of compound 1 in PI3Kgamma was solved revealing a binding mode in agreement with the SAR observed on PI3Kbeta. These compounds displayed inhibition in the nanomolar range in the biochemical assay and were also potent p-Akt inhibitors in a PTEN-deficient PC3 prostate cancer cell line. Optimization of in vitro pharmocokinetic properties led to compound 25 exhibiting 52% bioavailability in mice and target engagement in an acute PK/PD study. Preparation and optimization of new 4-(morpholin-4-yl)-(6-oxo-1,6-dihydropyrimidin-2-yl)amide derivatives as PI3Kbeta inhibitors.,Certal V, Halley F, Virone-Oddos A, Thompson F, Filoche-Romme B, El-Ahmad Y, Carry JC, Delorme C, Karlsson A, Abecassis PY, Vincent L, Bonnevaux H, Nicolas JP, Morales R, Michot N, Vade I, Louboutin A, Perron S, Doerflinger G, Tric B, Monget S, Lengauer C, Schio L Bioorg Med Chem Lett. 2012 Oct 15;22(20):6381-4. doi: 10.1016/j.bmcl.2012.08.072., Epub 2012 Aug 25. PMID:22981333 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-Kinases

Proteopedia Page Contributors and Editors (what is this?)

OCA