Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity

@article{Sarvagalla2015IdentificationOL,
  title={Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity},
  author={Sailu Sarvagalla and Vivek Kumar Singh and Yi-Yu Ke and Hui-Yi Shiao and Wen-Hsing Lin and H. I. Hsieh and John T. A. Hsu and Mohane Selvaraj Coumar},
  journal={Journal of computer-aided molecular design},
  year={2015},
  volume={29 1},
  pages={89-100}
}
Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as… CONTINUE READING
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