Skipping of exon 51, which targets up to 13% of patients, represents the monoskipping therapy which would be applicable to the largest proportion of DMD patients. Antisense molecules, delivered either intravenously or sub-cutaneously, have shown some restoration of dystrophin to a variable degree in patients. Next generation trials are planned with constructs which increase the efficiency of delivery of the antisense oligonucleotides. The efficacy of this approach was demonstrated using the dystrophin/utrophin knockout mouse, where restoration of muscle function was demonstrated. To treat more patients, different antisense sequences will need to be developed to target other exons and the regulatory authorities may treat each of these new constructs as a new drug. The ideal scenario would be to develop multi-exon skipping but this may only be achieved using AAV delivery which faces immunological problems. We have taken an alternative pharmacological approach to DMD by developing an orally bioavailable small molecule which should be appropriate to treat all patients irrespective of their mutation and target both skeletal and cardiac muscle. Building on our work in the mdx mouse, which demonstrated that the loss of dystrophin could be compensated for by increasing the levels of the dystrophin-related protein, utrophin, we have developed novel small molecules which can transcriptionally upregulate the utrophin gene. The demonstration that increased utrophin can reduce the muscular dystrophy in the mdx mouse has been confirmed by others. Our early data from the mdx mouse suggested that increasing the levels of utrophin over two-fold would be of great benefit. SMT C1100 was the final product of an exhaustive chemical screening and optimisation campaign. In this paper we present evidence confirming an overall two-fold increase in both utrophin RNA and protein resulting in a significant reduction in dystrophic symptoms and increased muscle function in dystrophin-deficient mdx mice. This was a U0126 comprehensive study looking at the beneficial effects of daily dosing of SMT C1100 in both sedentary mdx and the more severely affected forced exercise model. If the results obtained here using SMT C1100 translated across to DMD patients then undoubtedly this would be a disease modifying therapy for DMD. In order to confirm that SMT C1100 had no obvious off target toxicological liabilities mice were dosed with high levels of compound. Overall no toxicologically significant changes in clinical condition, body weight, food consumption, haematology or clinical chemistry parameters were seen during the study. There were no microscopic findings within the comprehensive set of tissues analysed due to effects of SMT C1100. Conclusion from Covance Laboratories Ltd. confirmed that the study did not identify any toxicity that was Vismodegib attributable to dosing with SMTC1100.