Current status and future directions of high-throughput ADME screening in drug discovery

Wilson Z. Shou

doi:10.1016/j.jpha.2020.05.004

The current status and future directions of hepatitis B antiviral drug discovery

Expert Opinion on Drug Discovery ◽

10.1080/17460441.2017.1255195 ◽

2016 ◽

Vol 12 (1) ◽

pp. 5-15 ◽

Cited By ~ 27

Author(s):

Liudi Tang ◽

Qiong Zhao ◽

Shuo Wu ◽

Junjun Cheng ◽

Jinhong Chang ◽

...

Keyword(s):

Drug Discovery ◽

Hepatitis B ◽

Antiviral Drug ◽

Current Status ◽

Future Directions

Download Full-text

High-Throughput Cellular Thermal Shift Assays in Research and Drug Discovery

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555219877183 ◽

2019 ◽

Vol 25 (2) ◽

pp. 137-147 ◽

Cited By ~ 2

Author(s):

Mark J. Henderson ◽

Marc A. Holbert ◽

Anton Simeonov ◽

Lorena A. Kallal

Keyword(s):

Drug Discovery ◽

High Throughput ◽

Microtiter Plate ◽

Target Engagement ◽

Biochemical Activity ◽

Future Directions ◽

Protein Target ◽

High Throughput Screens ◽

Beta Galactosidase ◽

Thermal Shift

Thermal shift assays (TSAs) can reveal changes in protein structure, due to a resultant change in protein thermal stability. Since proteins are often stabilized upon binding of ligand molecules, these assays can provide a readout for protein target engagement. TSA has traditionally been applied using purified proteins and more recently has been extended to study target engagement in cellular environments with the emergence of cellular thermal shift assays (CETSAs). The utility of CETSA in confirming molecular interaction with targets in a more native context, and the desire to apply this technique more broadly, has fueled the emergence of higher-throughput techniques for CETSA (HT-CETSA). Recent studies have demonstrated that HT-CETSA can be performed in standard 96-, 384-, and 1536-well microtiter plate formats using methods such as beta-galactosidase and NanoLuciferase reporters and AlphaLISA assays. HT-CETSA methods can be used to select and characterize compounds from high-throughput screens and to prioritize compounds in lead optimization by facilitating dose–response experiments. In conjunction with cellular and biochemical activity assays for targets, HT-CETSA can be a valuable addition to the suite of assays available to characterize molecules of interest. Despite the successes in implementing HT-CETSA for a diverse set of targets, caveats and challenges must also be recognized to avoid overinterpretation of results. Here, we review the current landscape of HT-CETSA and discuss the methodologies, practical considerations, challenges, and applications of this approach in research and drug discovery. Additionally, a perspective on potential future directions for the technology is presented.

Download Full-text

Current status, problems, and future directions of bioinformatics for drug discovery

Folia Pharmacologica Japonica ◽

10.1254/fpj.129.51 ◽

2007 ◽

Vol 129 (1) ◽

pp. 51-55

Author(s):

Hiroki Shirai ◽

Masato Kobori

Keyword(s):

Drug Discovery ◽

Current Status ◽

Future Directions

Download Full-text

Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies

Journal of Immunology Research ◽

10.1155/2014/315179 ◽

2014 ◽

Vol 2014 ◽

pp. 1-18 ◽

Cited By ~ 56

Author(s):

Michael Mahler ◽

Pier-Luigi Meroni ◽

Xavier Bossuyt ◽

Marvin J. Fritzler

Keyword(s):

Rheumatic Diseases ◽

High Throughput ◽

Indirect Immunofluorescence ◽

Solid Phase ◽

Ease Of Use ◽

Current Status ◽

Digital Reading ◽

Comprehensive Overview ◽

Future Directions ◽

Autoimmune Rheumatic Diseases

The detection of autoantibodies that target intracellular antigens, commonly termed anti-nuclear antibodies (ANA), is a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). Different methods are available for detection of ANA and all bearing their own advantages and limitations. Most laboratories use the indirect immunofluorescence (IIF) assay based on HEp-2 cell substrates. Due to the subjectivity of this diagnostic platform, automated digital reading systems have been developed during the last decade. In addition, solid phase immunoassays using well characterized antigens have gained widespread adoption in high throughput laboratories due to their ease of use and open automation. Despite all the advances in the field of ANA detection and its contribution to the diagnosis of SARD, significant challenges persist. This review provides a comprehensive overview of the current status on ANA testing including automated IIF reading systems and solid phase assays and suggests an approach to interpretation of results and discusses meeting the problems of assay standardization and other persistent challenges.

Download Full-text