Metabolic stability is an important property of drug candidates and pharmaceutical companies often have human liver microsomal (HLM) data for a large number of molecules, enabling development of global quantitative structure-activity relationship models.
Results: This study describes a strategy for building a global HLM quantitative structure-activity relationship model, applicable also to datasets of limited size. By using external congeneric test sets, a realistic description of the performance in the future applied setting and a reliable prediction confidence method is obtained.
Conclusion: The limited ability of the HLM model to generalize in chemical space to show the importance of internal model development and continuous updating of global HLM models, as well as the importance of a validated prediction confidence method.
Keywords: HLM; QSAR; prediction confidence.