Cluster Enrichment Method to Identify Inhibitors of Down-Regulators of Immune Signaling in a Kinetic High-Throughput Screening Assay

• Activity Number: 38
• Type: Contributed
• Date/Time: Sunday, July 31, 2016 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Minya Pu* and Karen Messer and Howard Cottam and Tomoko Hayashi and Maripat Corr and Dennis Carson
• Companies: University of California at San Diego and University of California at San Diego and University of California at San Diego and University of California at San Diego and University of California at San Diego and University of California at San Diego
• Keywords: Cluster enrichment ; High-throughput screening (HTS) ; Murcko classes ; Daylight-style fingerprint ; Top X approach ; Mixture model

Abstract

A cell-based kinetic high-throughput screening (HTS) assay was performed to identify compounds that induce sustained immune signaling. A previously defined statistical/chemoinformatic approach was used to identify hits. This new independent data set allowed us to assess the performance of the method. Assay parameters were determined in the pilot screen. Multiple controls were placed on each plate. The primary screen used ~167,000 compounds to identify ~2000 active substances ('hits') to carry forward to the confirmation screen. Two chemoinformatic approaches and a standard approach were tried: Murcko classes identified 445 hits, Daylight-style fingerprint clusters 1162 hits, and Top X approach 600 hits. Confirmation rates calculated using a mixture model approach were 30.8%, 20.2% and 18.6% respectively. These data showed that the cluster enrichment method we developed worked well for this more complicated kinetic HTS assay.