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ID: ALA4842386

Journal: J Med Chem

Title: Discovery of Reldesemtiv, a Fast Skeletal Muscle Troponin Activator for the Treatment of Impaired Muscle Function.

Authors: Collibee SE, Bergnes G, Chuang C, Ashcraft L, Gardina J, Garard M, Jamison CR, Lu K, Lu PP, Muci A, Romero A, Valkevich E, Wang W, Warrington J, Yao B, Durham N, Hartman J, Marquez A, Hinken A, Schaletzky J, Xu D, Hwee DT, Morgans D, Malik FI, Morgan BP.

Abstract: The discovery of reldesemtiv, a second-generation fast skeletal muscle troponin activator (FSTA) that increases force production at submaximal stimulation frequencies, is reported. Property-based optimization of high throughput screening hit 1 led to compounds with improved free exposure and in vivo muscle activation potency compared to the first-generation FSTA, tirasemtiv. Reldesemtiv demonstrated increased muscle force generation in a phase 1 clinical trial and is currently being evaluated in clinical trials for the treatment of amyotrophic lateral sclerosis.

CiteXplore: 34636234

DOI: 10.1021/acs.jmedchem.1c01067