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NIH Research Festival

September 13 – 15, 2017

Identification of acetylcholinesterase inhibitors using homogenous cell-based assays in quantitative high-throughput screening platforms

Thursday, September 14, 2017 – Poster Session III
12:00 – 1:30 p.m.

FAES Terrace

NCATS

NEURO-2

Authors

  • SZ Li
  • RL Huang
  • S Solomon
  • YL Liu
  • Bin Zhao
  • MF Santillo
  • MH Xia

Abstract

Acetylcholinesterase (AChE) is an enzyme responsible for metabolism of acetylcholine, a neuro- transmitter associated with muscle movement, cognition, and other neurobiological processes. Inhibition of AChE activity can serve as a therapeutic mechanism, but also cause adverse health effects and neurotoxicity. In order to efficiently identify AChE inhibitors from large compound libraries, homogenous cell-based assays in high-throughput screening platforms are needed. In this study, a fluorescent method using Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine) and the Ellman absorbance method were both developed in a homogenous format using a human neuro- blastoma cell line (SH-SY5Y). An enzyme-based assay using Amplex Red was also optimized and used to confirm the potential inhibitors. These three assays were used to screen 1368 compounds, which included a library of pharmacologically active compounds (LOPAC) and 88 additional com- pounds from the Tox21 program, at multiple concentrations in a quantitative high-throughput screening (qHTS) format. All three assays exhibited exceptional performance characteristics including assay signal quality, precision, and reproducibility. A group of inhibitors were identified from this study, including known (e.g. physostigmine and neostigmine bromide) and potential novel AChE inhibitors (e.g. chelerythrine chloride and cilostazol). These results demonstrate that this platform is a promising means to profile large numbers of chemicals that inhibit AChE activity.

Scientific Focus Area: Neuroscience

This page was last updated on Friday, March 26, 2021

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Current Research Festival

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  • 2024
    • General Schedule of Events
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    • Special Wednesday Events
    • Vendor Exhibit Information
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  • 2023
    • General Schedule of Events
    • NIH Early–Career Investigator Lectures
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    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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  • 2018
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    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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  • 2017
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
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