4jai

Crystal Structure of Aurora Kinase A in complex with N-{4-[(6-oxo-5,6-dihydrobenzo[c][1,8]naphthyridin-1-yl)amino]phenyl}benzamide

Structural highlights 4jai 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: 4jaj Gene: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 (Homo sapiens) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2. Furthermore, this compound inhibited phosphorylation of histone H3 (pHH3) in mouse bone morrow upon oral administration, which is consistent with inhibition of Aurora kinase B activity. SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors.,Karra S, Xiao Y, Chen X, Liu-Bujalski L, Huck B, Sutton A, Goutopoulos A, Askew B, Josephson K, Jiang X, Shutes A, Shankar V, Noonan T, Garcia-Berrios G, Dong R, Dhanabal M, Tian H, Wang Z, Clark A, Goodstal S Bioorg Med Chem Lett. 2013 May 15;23(10):3081-7. doi: 10.1016/j.bmcl.2013.03.008., Epub 2013 Mar 13. PMID:23570792 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase

spinqualitylabelsall models 4jai, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image