Identification of false positives in "HTS hits to lead": The application of Bayesian models in HTS triage to rapidly deliver a series of selective TRPV4 antagonists

Herein, we describe the discovery and optimisation of a series of potent and selective TRPV4 antagonists. The application of a variety of computational techniques (including Bayesian modelling) at the HTS triage stage enabled the early deprioritisation of likely frequent hitters. The use of methods...

Full description

Saved in:
Bibliographic Details
Published inMedChemComm Vol. 4; no. 1; pp. 244 - 251
Main Authors Skerratt, Sarah E, Mills, James E. J, Mistry, Jayesh
Format Journal Article
LanguageEnglish
Published 01.01.2013
Online AccessGet full text

Cover

More Information
Summary:Herein, we describe the discovery and optimisation of a series of potent and selective TRPV4 antagonists. The application of a variety of computational techniques (including Bayesian modelling) at the HTS triage stage enabled the early deprioritisation of likely frequent hitters. The use of methods to positively prioritise compounds for follow-up screening allowed the rapid identification of a number of interesting TRPV4 antagonist series. The hit-to-lead efforts in one such series, the hydroxypiperidines, will be described. The use of computational techniques to remove frequent hitters and enable the identification of a number of TRPV4 series from an HTS campaign will be described. The hit-to-lead efforts in one such series will also be discussed.
ISSN:2040-2503
2040-2511
DOI:10.1039/c2md20259j