Category: Assay Development and Screening

1203-D - The Application of Label-free Technologies in Triaging BACE Screening Hits

Tuesday, February 6, 2018
5:00 PM - 6:00 PM

    The hallmark of Alzheimer’s disease is the extracellular deposition of insoluble amyloid plaques in the brain.  β- and γ-Secretase are responsible for generating pathogenic Aß40 and Aß42 peptides that form the plaques.
    β–Secretase (BACE) is a transmembrane protein that belongs to the aspartyl protease family.  To date, more than 2.0-million compounds have been screened at Amgen against BACE in numerous campaigns.  The triage of BACE screening hits has proven to be extremely challenging due to the large number of false positives.
    Here we present two label-free assays to efficiently rule out the false positives from a screen of 474,600 compounds.  These two assays are 1) BACE Rapidfire Mass Spec assay, 2) BACE / reference protein multiplex SPR (Surface Plasmon Resonance) direct binding assay. All hits were triaged using these two assays, but none of the compounds were identified to be bona fide BACE inhibitors; the exception were three compounds that originated from the internal medicinal chemistry program and had been added to the screening collection.

Kui Chen

Amgen, Inc.
Thousand Oaks, CA

Kui Chen (“Kathy”) has been working in Amgen for more than 20 years. Her specialties are biochemical assay development, optimization and high-throughput screening. She focuses on enzymatic and binding assays in a variety of assay formats (fluorescence, luminescence, radioisotope, RapidFire high-throughput QQQ and QTOF Mass Spec system). She supports the Med-Chem and crystallography efforts for lead identification and optimization across various therapeutic areas, including Neuroscience, Cancer biology, Metabolic Disorder, and Inflammation.