5is5 | pdb_00005is5

Discovery and Pharmacological Characterization of Novel Quinazoline-based PI3K delta-selective Inhibitors

spinqualitylabelsall models 5is5, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5is5 is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6CY Gene: Pik3cd (LK3 transgenic mice) Activity: Phosphatidylinositol-4,5-bisphosphate 3-kinase, with EC number 2.7.1.153 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Inhibition of the lipid kinase PI3Kdelta is a promising principle to treat B and T cell driven inflammatory diseases. Using a scaffold deconstruction-reconstruction strategy, we identified 4-aryl quinazolines that were optimized into potent PI3Kdelta isoform selective analogues with good pharmacokinetic properties. With compound 11, we illustrate that biochemical PI3Kdelta inhibition translates into modulation of isoform-dependent immune cell function (human, rat, and mouse). After oral administration of compound 11 to rats, proximal PD markers are inhibited, and dose-dependent efficacy in a mechanistic plaque forming cell assay could be demonstrated. Discovery and Pharmacological Characterization of Novel Quinazoline-Based PI3K Delta-Selective Inhibitors.,Hoegenauer K, Soldermann N, Stauffer F, Furet P, Graveleau N, Smith AB, Hebach C, Hollingworth GJ, Lewis I, Gutmann S, Rummel G, Knapp M, Wolf RM, Blanz J, Feifel R, Burkhart C, Zecri F ACS Med Chem Lett. 2016 Jun 2;7(8):762-7. doi: 10.1021/acsmedchemlett.6b00119., eCollection 2016 Aug 11. PMID:27563400 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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