Category: Assay Development and Screening
Accumulation of aggregated alpha synuclein (aSYN) in the form of Lewy bodies is the pathological hallmark of Parkinson’s disease (PD). In vivo imaging of the aSYN aggregates with a radiotracer will become a very useful tool for early PD diagnoses, tracking of disease progression and monitoring treatment efficacy. The objective is to develop a high-throughput screening (HTS) assay to identify small molecules that selectively bind to aSYN aggregates. Conventional filtration binding assays are time consuming, labor intensive, and often low throughput making them a sub-optimal choice for large scale compound screening. We have developed a competitive binding assay amenable to HTS in a scintillation proximity assay (SPA) format. This 384-well SPA assay exhibits saturable, competitive binding specific to aSYN aggregates and robust assay metrics. The assay was used to screen an in-house library consisting of 260K compounds. The screen has yielded several new structural series to enable SAR and a potential path to develop a PET ligand for PD treatment and diagnoses.
Qifeng Yang– Senior Scientist, Merck & Co., Inc, Kenilworth, New Jersey
Merck & Co., Inc
Kenilworth, New Jersey
I have extensive research experiences in pharmaceutical industry in the fields of molecular biology, biochemistry, cell biology and immunology. I have been working on screening now and am interested in HTS and automation technology.