NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds.

ABSTRACT:

Aim

Fragment-based lead discovery (FBLD) is a complementary approach in drug research and development. In this study, we established an NMR-based FBLD platform that was used to screen novel scaffolds targeting human bromodomain of BRD4, and investigated the binding interactions between hit compounds and the target protein.

Methods

1D NMR techniques were primarily used to generate the fragment library and to screen compounds. The inhibitory activity of hits on the first bromodomain of BRD4 [BRD4(I)] was examined using fluorescence anisotropy binding assay. 2D NMR and X-ray crystallography were applied to characterize the binding interactions between hit compounds and the target protein.

Results

An NMR-based fragment library containing 539 compounds was established, whi

SUBMITTER: Yu JL 

PROVIDER: S-EPMC4933754 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature