In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib.

ABSTRACT: Off-target pharmacology may contribute to both adverse and beneficial effects of a new drug. In vitro pharmacological profiling is often applied early in drug discovery; there are fewer reports addressing the relevance of broad profiles to clinical adverse effects. Here, we have characterized the pharmacological profile of the active metabolite of fostamatinib, R406, linking an understanding of drug selectivity to the increase in blood pressure observed in clinical studies. R406 was profiled in a broad range of in vitro assays to generate a comprehensive pharmacological profile and key targets were further investigated using functional and cellular assay systems. A combination of traditional literature searches and text-mining approaches established potential mechanistic links between the

SUBMITTER: Rolf MG 

PROVIDER: S-EPMC4618646 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature