Aini Vuorinen, Isabel V L Wilkinson, Maria Chatzopoulou, Ben Edwards, Sarah E Squire, Rebecca J Fairclough, Noelia Araujo Bazan, Josh A Milner, Daniel Conole, James R Donald, Nandini Shah, Nicky J Willis, R Fernando Martínez, Francis X Wilson, Graham M Wynne, Stephen G Davies, Kay E Davies, Angela J Russell
Duchenne muscular dystrophy is a fatal disease with no cure, caused by lack of the cytoskeletal protein dystrophin. Upregulation of utrophin, a dystrophin paralogue, offers a potential therapy independent of mutation type. The failure of first-in-class utrophin modulator ezutromid/SMT C1100 in Phase II clinical trials necessitates development of compounds with better efficacy, physicochemical and ADME properties and/or complementary mechanisms. We have discovered and performed a preliminary optimisation of a novel class of utrophin modulators using an improved phenotypic screen, where reporter expression is derived from the full genomic context of the utrophin promoter...
April 20, 2021: European Journal of Medicinal Chemistry