1432308-22-9Relevant academic research and scientific papers
SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors
Karra, Srinivasa,Xiao, Yufang,Chen, Xiaoling,Liu-Bujalski, Lesley,Huck, Bayard,Sutton, Amanda,Goutopoulos, Andreas,Askew, Ben,Josephson, Kristopher,Jiang, Xuliang,Shutes, Adam,Shankar, Vikram,Noonan, Tom,Garcia-Berrios, Gaianne,Dong, Rong,Dhanabal, Mohanraj,Tian, Hui,Wang, Zhenxiong,Clark,Goodstal, Samantha
, p. 3081 - 3087 (2013/06/26)
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.
