Solubility prediction in the bRo5 chemical space: where are we right now?

Giuseppe Ermondi; Vasanthanathan Poongavanam; Maura Vallaro; Jan Kihlberg; Giulia Caron

doi:10.5599/admet.834

Authors

Giuseppe Ermondi Department of Molecular Biotechnology and Health Sciences, University of Torino, Quarello 15, 10135, Torino, Italy
Vasanthanathan Poongavanam Department of Chemistry - BMC, Uppsala University, SE-75123, Uppsala, Sweden
Maura Vallaro Department of Molecular Biotechnology and Health Sciences, University of Torino, Quarello 15, 10135, Torino, Italy
Jan Kihlberg Department of Chemistry - BMC, Uppsala University, SE-75123, Uppsala, Sweden
Giulia Caron Department of Molecular Biotechnology and Health Sciences, University of Torino, Quarello 15, 10135, Torino, Italy

DOI:

https://doi.org/10.5599/admet.834

Abstract

Modelling the solubility of compounds in the “beyond Rule of 5” (bRo5) chemical space is in its infancy and to date only a few studies have been reported in the literature. Based on our own results, and those already published, we conclude that consideration of conformational flexibility and chameleon like behavior is important, but quantitative models that account for these properties remain to be developed. Inclusion of 3D information appears to be somewhat less important than for cell permeability and extremely challenging due to the difficulties of accurate conformational sampling in the bRo5 space. Currently, methods for modelling of solubility will have to be tailored to the set of investigated compounds.