Sturdy or Go Bust” Available Now

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, MD, 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 complementing the December issue of SLAS technology, a special collection entitled “Assay Guidance Manual for Drug Discovery: Technologies that Matter”.

Considerable efforts have been made over the past two decades within the biomedical science community to address the crisis of irreproducibility in basic and preclinical research. This special issue focuses on the Trial Guidance Workshops for High Throughput Screening and Lead Discovery conducted by the National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM). The articles in this issue expand on the workshop discussions by incorporating best practices into trial 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 AGA Workshop Series, members of the AGA Editorial Board and authors of the manual. Articles cover a wide range of topics, but focus on: best practices in assay development, data analysis, and implementation for high-throughput screening (HTS) and lead discovery; test development; and the validation and utility of specialized assays in lead discovery and target validation.

In Born’s article et al, the authors provide the medicinal chemist’s perspective on the importance of assay design to successful chemistry efforts. By providing case studies from the NCATS division of preclinical innovation and the literature, the team not only highlights the critical role of test design, but also opens a much-needed dialogue between biologists and chemists. Riss et al provides a broad overview of good cell culture practices and standard operating procedures for handling cultures while Korch et al highlight the problem of misidentification of cell lines and its enormous detrimental impact if left undetected. Both perspectives provide tools and resources for readers to address this issue.

The second general theme of this special issue includes original research articles that cover in vitro development and validation of assays as well as silicone validation of predictive models for ADME. Kaur et al present the development, optimization and validation of a new complex tumor spheroid assay for HTS. This article provides an example of the steps required to properly develop and validate 3D tumor spheroid models for pancreatic cancer. On the other hand, Wen et al highlights lessons learned from a failed trial development campaign to discover small molecules that can repair radiation damage.

The final topic area contains articles that focus on the usefulness 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 multi-target kinase inhibitor. Li et al describes the utility of an enzyme butyrylcholinesterase (BChE)-based inhibition assay for high-throughput, quantitative screening of nearly 9,000 chemical compounds to quickly and efficiently identify potential BChE inhibitors.

This special issue of SLAS Discovery includes six original research papers:

  • Address unusual assay variability with robust statistics
  • Complex tumor spheroids, a tissue-mimicking tumor model, for drug discovery and precision medicine
  • ‘Failed’ trial development for discovery of rescue of small molecules from radiation damage
  • Validation of ADME QSAR models using marketed drugs
  • Phenotypic screening after transcriptomic deconvolution to identify transcription factors mediating kinase inhibitor-induced axon outgrowth
  • Identification of compounds for butyrylcholinesterase inhibition

Other articles in this issue include:

  • Guidance Manual for Drug Discovery Trials: Rise or Collapse
  • The Impact of Test Design on Medicinal Chemistry: Case Studies
  • Treat cells as reagents to design reproducible assays
  • The widespread and costly impacts of HEp-2 [HeLa], intestine 407 [HeLa], and other fake cell lines in journal publications
  • Addressing Compound Reactivity Interference and Aggregation Testing: 1280 Case Studies of High-Throughput Biochemical Screening Campaigns Benefiting from National Institutes of Health Testing Guidance Manual Guidelines

Access this SLAS Discovery the 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 science researchers, developers and suppliers of laboratory automation technologies. The mission of SLAS is to bring together researchers from academia, industry and government to advance life science discovery and technology through education, knowledge exchange and global community building. .

SLAS Discovery: advancing the science of drug discovery, Impact factor 2019 2.918. Editor-in-Chief Robert M. Campbell, Ph.D., Twentyeight-Seven Therapeutics, Boston, MA (USA)

SLAS technology: translating innovation into life sciences, 2019 Impact Factor 3.047. Editor-in-Chief Edward Kai-Hua Chow, Ph.D., National University of Singapore (Singapore).

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About Irene J. O'Donnell

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