A "Failed" Assay Development for the Discovery of Rescuing Small Molecules from the Radiation Damage

Kuo-Kuang Wen; Stephen Roy; Isabella M. Grumbach; Meng Wu

doi:10.1177/24725552211020678

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A "Failed" Assay Development for the Discovery of Rescuing Small Molecules from the Radiation Damage

Journal article

Open access

Peer reviewed

A "Failed" Assay Development for the Discovery of Rescuing Small Molecules from the Radiation Damage

Kuo-Kuang Wen, Stephen Roy, Isabella M. Grumbach and Meng Wu

SLAS discovery, Vol.26(10), pp.1315-1325

12/01/2021

DOI: 10.1177/24725552211020678

PMCID: PMC8612958

PMID: 34151632

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Abstract

With improving survival rates for cancer patients, the side effects of radiation therapy, especially for pediatric or more sensitive adult patients, have raised interest in preventive or rescue treatment to overcome the detrimental effects of efficient radiation therapies. For the discovery of rescuing small molecules for radiation damage to the endothelium, we have been developing a 96-well microplate-based in vitro assay for high-throughput compatible measurement of radiation-induced cell damage and its rescue by phenotypic high-content imaging. In contrast to traditional radiation assays with detached cells for clonogenic formation, we observed cells with live-cell imaging in two different kinds of endothelial cells, up to three different cell densities, two gamma-infrared radiation dose rates, more than four different radiation doses, and acute (within 24 h with one to two h intervals) and chronic (up to 7 days) responses by phenotypic changes (digital phase contrast) and functional assays (nuclear, live-cell, and dead-cell staining) at the end of the assay. Multiple potential small molecules, which have been reported for rescuing radiation damage, have been tested as assay controls with dose responses. At the end, we did not move ahead with the pilot screening. The lessons learned from this "failed" assay development are shared.

Biochemical Research Methods

Biochemistry & Molecular Biology

Biotechnology & Applied Microbiology

Chemistry

Chemistry, Analytical

Life Sciences & Biomedicine

Physical Sciences

Science & Technology

Details

Title: Subtitle: A "Failed" Assay Development for the Discovery of Rescuing Small Molecules from the Radiation Damage
Creators: Kuo-Kuang Wen - University of Iowa
Stephen Roy - University of Iowa
Isabella M. Grumbach - Roy J. and Lucille A. Carver College of Medicine
Meng Wu - University of Iowa
Resource Type: Journal article
Publication Details: SLAS discovery, Vol.26(10), pp.1315-1325
DOI: 10.1177/24725552211020678
PMID: 34151632
PMCID: PMC8612958
NLM abbreviation: SLAS Discov
ISSN: 2472-5552
eISSN: 2472-5560
Publisher: Elsevier
Number of pages: 11
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: I01BX000163; DOI: 10.13039/100000002, name: National Institutes of Health, award: P30CA086862; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01EY031544; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL108932; DOI: 10.13039/100000002, name: National Institutes of Health, award: R50CA243786; DOI: 10.13039/100000002, name: National Institutes of Health, award: S10 RR029274
Language: English
Date published: 12/01/2021
Academic Unit: Pharmacy; Stead Family Department of Pediatrics; Cardiovascular Medicine; Radiation Oncology; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984359881102771

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