The impact of binding site waters on the activity/selectivity trade-off of Janus kinase 2 (JAK2) inhibitors.
Basic Information
ID: ALA4480435
Journal: Bioorg Med Chem
Title: The impact of binding site waters on the activity/selectivity trade-off of Janus kinase 2 (JAK2) inhibitors.
Authors: Egyed A, Bajusz D, Keserű GM.
Abstract: Structure based optimization of B39, an indazole-based low micromolar JAK2 virtual screening hit is reported. Analysing the effect of certain modifications on the activity and selectivity of the analogues suggested that these parameters are influenced by water molecules available in the binding site. Simulation of water networks in combination with docking enabled us to identify the key waters and to optimize our primary hit into a low nanomolar JAK2 lead with promising selectivity over JAK1.
CiteXplore: 30833158
DOI: 10.1016/j.bmc.2019.02.029
Patent ID: ┄