4 research outputs found

    Additional file 2: Figure S1. of Deletion of the Ste20-like kinase SLK in skeletal muscle results in a progressive myopathy and muscle weakness

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    SLK knockout mice display reduced body mass, muscle size, but show no increase in fibrosis. (A) Body mass of wild type and knockout littermates was measured from 4 weeks to 22 weeks (n = 5/genotype). (B) Fiber cross-sectional area was measured in wild type and knockout mice at 3 and 24 weeks (n = 5/genotype). (C) Western blot for markers of fibrosis and atrophy on 6-month-old skeletal muscle lysates. (D, E) Masson’s trichome staining on 6-month-old skeletal muscle cross sections from wild type and knockout muscle. (TIF 5209 kb

    Process Development and Optimization for Production of a Potassium Ion Channel Blocker, ICA-17043

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    A scalable process for the manufacture of a potassium ion channel blocker was developed and optimized. Key features of the process include an optimized Grignard reaction, a direct cyanation of the intermediate trityl alcohol derivative, and an improved nitrile hydrolysis protocol, relative to the original acidic hydrolysis conditions, to generate the crude active pharmaceutical ingredient (API) with >95% HPLC purity. The Grignard and the cyanation reactions could be telescoped, resulting in an improved throughput compared to the original four-step process. An effective recrystallization of the API was also developed and the process scaled up to manufacture multiple batches at the pilot scale

    Process Development and Optimization for Production of a Potassium Ion Channel Blocker, ICA-17043

    No full text
    A scalable process for the manufacture of a potassium ion channel blocker was developed and optimized. Key features of the process include an optimized Grignard reaction, a direct cyanation of the intermediate trityl alcohol derivative, and an improved nitrile hydrolysis protocol, relative to the original acidic hydrolysis conditions, to generate the crude active pharmaceutical ingredient (API) with >95% HPLC purity. The Grignard and the cyanation reactions could be telescoped, resulting in an improved throughput compared to the original four-step process. An effective recrystallization of the API was also developed and the process scaled up to manufacture multiple batches at the pilot scale
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