Notes: This review delves into the drug discovery pipeline, focusing on both phenotypic drug discovery (PDD) and target-based drug discovery (TDD) and the importance of experiments which determine the mechanism of action (MOA) of drugs. NanoBRET is highlighted as a highly specific assay for the measurement of target interaction. Specifically, the precise tagging of a target greatly minimizes assay cross-talk. (5122)

Notes: Activation of Notch isoforms via histone deacetylase inhibitors (HDACi) has been shown to suppress neuroendocrine (NE) cancers. Here, a novel HDACi called thailandepsin A (TDP-A) was characterized and shown to induce cell cycle arrest and apoptosis. The NanoBRET Target Engagement system was used to determine TDP-A binding to HDAC1. TT cells expressing an HDAC1-NanoLuc fusion were treated with TDP-A and competed HDAC tracer compound to determine in vivo binding affinity.  (5131)

Notes: The authors describe a new method for real-time analysis of ligand-mediated receptor endocytosis in living cells. They used a BRET-based assay to detect the interactions of ligands with various GPCRs fused to NanoLuc® luciferase. (4693)

Notes: These authors describe a new method for monitoring ligand binding to GPCRs on the surface of living cells. They used NanoLuc luciferase in a BRET-based assay to detect the interactions of ligands with the receptors with an N-terminal NanoLuc fusion. (4589)

Notes: This paper describes a method for using bioluminescence resonance energy transfer (BRET) to reveal the binding characteristics of a drug with selected targets in live cells. The authors used cell-permeable fluorescent tracers in a competitive binding assay to quantify drug engagement with target proteins fused to Nanoluc luciferase. Using this approach, they were able to profile isozyme-specific engagement and binding kinetics for a panel of histone deacetylase (HDAC) inhibitors. (4587)