Abstract
Enzymes are common targets in high-throughput screening and related campaigns. An analysis of papers published between 1990 and 2018 showed that kinases were the most common enzymes investigated, fluorescence-based assays were the most common read-out method, and cancer and bacterial infections were the most common therapeutic areas. High-throughput screening and fragment-screening campaigns published between 2017 and 2019, were analyzed in more depth, giving 75 examples of hit to lead development. Kinases, phosphatases, proteases and peptidases were the most common targets, fluorescent assays were the most commonly used, and a wide variety of structural features were observed within the derived drugs. Hit frequency was largely independent of library size and positively correlated with Z’ value for the assay. Binding of metal ions to library compounds and substrates is an under-appreciated source of false-positive results and unreproducible behavior.
| Original language | English |
|---|---|
| Pages (from-to) | 10742–10772 |
| Number of pages | 31 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 63 |
| Issue number | 19 |
| Early online date | 20 May 2020 |
| DOIs | |
| Publication status | Published - 8 Oct 2020 |
Access to Document
- Paper13
This document is the Accepted Manuscript version of a Published Work that appeared in final form in J. Med. Chem., copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00523
- Supporting Information
This document is the Accepted Manuscript version of a Published Work that appeared in final form in J. Med. Chem., copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00523