Oak Brook, IL – The December edition of SLAS Discovery, “Assay Guidance Manual for Drug Discovery: Robust or Go Bust” by Guest Editors Sarine Markossian, Ph.D., G. Sitta Sittampalam, Ph.D., Jayme L. Dahlin, M.D., Ph.D., (National Center for Advancing Translational Sciences, NIH, Bethesda, MD, USA) and Nathan P. Coussens, Ph.D. (Frederick National Laboratory for Cancer Research, Frederick, MD, USA) is a Special Issue complimenting the December issue of SLAS Technology, a Special Collection entitled, “Assay Guidance Manual for Drug Discovery: Technologies that Matter.”
There have been considerable efforts in the last two decades within the biomedical science community to address the crisis of irreproducibility in basic and preclinical research. This special issue is focused on the Assay Guidance Workshops for High-Throughput Screening and Lead Discovery conducted by the National Center for Advancing Translational Sciences (NCATS)’s Assay Guidance Manual (AGM) program. The articles in this issue expand on workshop discussions by incorporating best practices in assay methodologies by illustrating how these discussed principles are critical to the entire drug development process.
Most of the articles in this issue are written by speakers from the AGM workshop series, members of the AGM’s editorial board and authors of the manual. The articles span a wide range of topics but are focused on: best practices in assay development, data analysis, and implementation for high-throughput screening (HTS) and lead discovery; assay development; and validation and the utility of specialized assays in lead discovery and target validation.
In the article by Born et al, the authors provide the medicinal chemist’s viewpoint on the importance of assay design for successful chemistry efforts. By providing case studies from both the NCATS division of preclinical innovation and the literature, the team not only highlights the critical role of assay design, but also opens a much-needed dialogue between biologists and chemists. Riss et al gives a broad overview of good cell culture practices and standard operating procedures for handling cultures while Korch et al highlight the problem of cell line misidentification and its enormous detrimental impact if left undetected. Both perspectives provide tools and resources for readers to address this issue.
The second general topic area of this special issue includes articles of original research that cover in vitro assay development and validation as well as in silico validation of predictive models for ADME. Kaur et al present the development, optimization, and validation of a novel complex tumor spheroid assay for HTS. This article provides an example of the steps needed to properly develop and validate 3D tumor spheroid models for pancreatic cancer. In contrast, Wen et al highlights lessons learned from a failed assay development campaign to discover small molecules that can rescue radiation damage.
The last topic area contains articles that focus on the utility of specialized assays in lead discovery and target validation. Lowell et al uses a combined transcriptomic-phenotypic screening strategy to identify novel transcriptional regulators of neurite outgrowth downstream of a multitarget kinase inhibitor. Li et al describes the utility of a butyrylcholinesterase (BChE) enzyme-based inhibition assay for a quantitative high-throughput screen of nearly 9,000 chemical compounds to identify potential BChE inhibitors rapidly and efficiently.
This Special Issue of SLAS Discovery includes six articles of original research:
- Addressing Unusual Assay Variability with Robust Statistics
- Complex Tumor Spheroids, a Tissue-Mimicking Tumor Model, for Drug Discovery and Precision Medicine
- A “Failed” Assay Development for the Discovery of Rescuing Small Molecules from the Radiation Damage
- Validating ADME QSAR Models Using Marketed Drugs
- Phenotypic Screening Following Transcriptomic Deconvolution to Identify Transcription Factors Mediating Axon Growth Induced by a Kinase Inhibitor
- Identification of Compounds for Butyrylcholinesterase Inhibition
Other articles in this issue include:
- Assay Guidance Manual for Drug Discovery: Robust or Go Bust
- The Impact of Assay Design on Medicinal Chemistry: Case Studies
- Treating Cells as Reagents to Design Reproducible Assays
- The Extensive and Expensive Impacts of HEp-2 [HeLa], Intestine 407 [HeLa], and Other False Cell Lines in Journal Publications
- Addressing Compound Reactivity and Aggregation Assay Interferences: 1280 Case Studies of Biochemical High-Throughput Screening Campaigns Benefiting from the National Institutes of Health Assay Guidance Manual Guidelines
Access to this SLAS Discovery issue is available at https://journals.sagepub.com/toc/jbxb/current
For more information about SLAS and its journals, visit https://www.slas.org/publications
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SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.
SLAS Discovery: Advancing the Science of Drug Discovery, 2019 Impact Factor 2.918. Editor-in-Chief Robert M. Campbell, Ph.D., Twentyeight-Seven Therapeutics, Boston, MA (USA)
SLAS Technology: Translating Life Sciences Innovation, 2019 Impact Factor 3.047. Editor-in-Chief Edward Kai-Hua Chow, Ph.D., National University of Singapore (Singapore).
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