Chun Hwa Chen

TL;DR: HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19, which inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFRKinase at nanomolar concentration.

TL;DR: Structural insights obtained from the EGFR/2a complex suggested that an extension from the meta-position on the phenyl group (ring-5) would improve interactions with the DFG motif, and introduction of an N,N-dimethylamino tail resulted in 4b, which showed almost 50-fold improvement in inhibition compared to 2a.

TL;DR: Through structure-based virtual screening, novel pyrazole hit 8a was identified as Aurora kinase A inhibitor and compound 12w showed selective inhibition of Aurora A kinase over Aurora B/C, which might be due to the presence of a unique H-bond interaction between the 3-acetamido group and the Aurora A nonconserved Thr217 residue.

TL;DR: Molecular dynamics simulation and density functional theory calculation suggest that BPR056 interacted with FLT3 in a stable manner and could be chemically optimized to realize a drug-like lead in the future.

TL;DR: A simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in‐house compound library to select compounds for testing is revealed.