BioDash: A semantic web dashboard for drug development
Eric K. Neumann, Dennis Quan
PSB 2006
The human Aurora kinase-A (AK-A) is an essential mitotic regulator that is frequently overexpressed in several cancers. The recent development of several novel AK-A inhibitors has been driven by the well-established association of this target with cancer development and progression. However, resistance and cross-reactivity with similar kinases demands an improvement in our understanding of key molecular interactions between the Aurora kinase-A substrate binding pocket and potential inhibitors. Here, we describe the implementation of state-of-the-art virtual screening techniques to discover a novel set of Aurora kinase-A ligands that are predicted to strongly bind not only to the wild type protein, but also to the T217D mutation that exhibits resistance to existing inhibitors. Furthermore, a subset of these computationally screened ligands was shown to be more selective toward the mutant variant over the wild type protein. The description of these selective subsets of ligands provides a unique pharmacological tool for the design of new drug regimens aimed at overcoming both kinase cross-reactivity and drug resistance associated with the Aurora kinase-A T217D mutation. © 2013 American Chemical Society.
Eric K. Neumann, Dennis Quan
PSB 2006
Gowri Nayar, Ignacio Terrizzano, et al.
Frontiers in Genetics
Wesam Alramadeen, Yu Ding, et al.
IISE Transactions on Healthcare Systems Engineering
Huajun Chen, Guotong Xie
Expert Opinion on Drug Discovery