Category: Assay Development and Screening
Aaron A. Nazarian1*, Soo Hang Wong1, Carlo J.van Staden1, Jessie St. Martin2, Steve Schneider2, Paul Andrews2, David Powers1 and Franck Madoux1 1Amgen Therapeutic Discovery / Discovery Technologies 2Amgen Neuroscience *Corresponding author: Aaron A. Nazarian, email@example.com
Amgen Inc., Thousand Oaks, CA
Ubiquitin plays a central role in mediating protein degradation. Screening for small molecule inhibitors of deubiquitinating (DUB) enzymes may have therapeutic potential for neurodegenerative disease. Here we describe a comprehensive small molecule screening campaign, utilizing our ultra high-throughput screening (UHTS) robotic platform to identify high quality, selective DUB inhibitors. We have developed, miniaturized and used a combination of four different assays to better ascertain the desired inhibition profile. Specifically, we identified primary hits with potential for interference through counter screen, by confirming bona fide activity independent of the detection technology via a competitive binding displacement TRF orthogonal assay, and by ensuring selectivity using a closely related DUB catalytic assay.
Aaron A. Nazarian1*, Soo Hang Wong1, Carlo J.van Staden1, Jessie St. Martin2, Steve Schneider2, Paul Andrews2, David Powers1 and Franck Madoux1
1Amgen Therapeutic Discovery / Discovery Technologies
*Corresponding author: Aaron A. Nazarian, firstname.lastname@example.org
Aaron Nazarian– Sr. Associate Scientist, Amgen, Thousand Oaks, CA
Sr. Associate Scientist
Thousand Oaks, CA
Aaron A. Nazarian is currently Senior Associate Scientist in Therapeutic Discovery at Amgen, where he has made important contributions to the discovery and characterization of various Amgen therapeutic candidates. Aaron has broad experience with assay development and miniaturization, high-throughput screening, and in vitro characterization for both large and small molecules. His strong analytical and automation skills have led to the successful development of binding and functional assays in the fields of G-protein-coupled receptors (GPCRs), ion channels and kinases.
Currently a core member of the Ultra High-Throughput Screening (UHTS) group within Discovery Technologies, Aaron directly contributes to multiple high-quality small molecule screening campaigns and was involved with the implementation of Amgen’s 1536-well format capable UHTS platform. In the Bioassay & Profiling group, Aaron enhanced Amgen’s biologics identification and characterization capabilities. Specifically, he developed a high-capacity T-cell dependent cellular cytotoxicity (TDCC) assay platform, screening over 15 Oncology targets and accelerating Amgen’s discovery pipeline of Bispecific T-Cell Engaging (BiTE) antibodies.
Prior to joining Amgen in 2005, Aaron conducted research studies to elucidate the molecular mechanisms of mammalian gene regulation in the immune system in the lab of Stephen T. Smale (UCLA/ HHMI). Aaron received his Bachelor of Science (BS) degree, magna cum laude, in Microbiology, Immunology & Molecular Genetics (MIMG) from The University of California, Los Angeles (UCLA) in 2003.