16690-22-5Relevant academic research and scientific papers
Biological Efficacy and Toxicity of Diamidines in Myotonic Dystrophy Type 1 Models
Siboni, Ruth B.,Bodner, Micah J.,Khalifa, Muhammad M.,Docter, Aaron G.,Choi, Jessica Y.,Nakamori, Masayuki,Haley, Michael M.,Berglund, J. Andrew
, p. 5770 - 5780 (2015)
Myotonic dystrophy type 1 (DM1) is a disease characterized by errors in alternative splicing, or "mis-splicing". The causative agent of mis-splicing in DM1 is an inherited CTG repeat expansion located in the 3′ untranslated region of the DM protein kinase gene. When transcribed, CUG repeat expansion RNA sequesters muscleblind-like (MBNL) proteins, which constitute an important family of alternative splicing regulators. Sequestration of MBNL proteins results in the mis-splicing of its regulated transcripts. Previous work has demonstrated that pentamidine, a diamidine which is currently FDA-approved as an antiparasitic agent, was able to partially reverse mis-splicing in multiple DM1 models, albeit at toxic concentrations. In this study, we characterized a series of pentamidine analogues to determine their ability to reverse mis-splicing and their toxicity in vivo. Experiments in cell and mouse models demonstrated that compound 13, also known as furamidine, effectively reversed mis-splicing with equal efficacy and reduced toxicity compared to pentamidine.
ARYL DIAMIDINES AND PRODRUGS THEREOF FOR TREATING MYOTONIC DYSTROPHY
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Page/Page column 0118; 0119, (2013/11/05)
Disclosed herein are compounds (for example, diamidine derivatives and prodrugs) and methods of use thereof, for example in treating muscular dystrophy (DM) or disease caused by a toxic RNA in a subject. In some embodiments, the methods include administering an effective amount of one of more of the disclosed compounds to a subject to treat or inhibit DM or a disease caused by or associated with toxic RNA, such as DM1, DM2, spinocerebellar ataxia type 8 (SCA8), fragile X tremor ataxia syndrome (FXTAS), or Huntington disease-like 2 (HLD2). In some examples, the methods include selecting a subject for treatment, for example selecting a subject with DM1, DM2, SCA8, FXTAS, or HLD2.
