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

Autor: Collibee SE; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Bergnes G; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Chuang C; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Ashcraft L; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Gardina J; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Garard M; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Jamison CR; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Lu K; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Lu PP; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Muci A; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Romero A; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Valkevich E; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Wang W; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Warrington J; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Yao B; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Durham N; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Hartman J; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Marquez A; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Hinken A; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Schaletzky J; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Xu D; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Hwee DT; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Morgans D; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Malik FI; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States., Morgan BP; Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California 94080, United States.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2021 Oct 28; Vol. 64 (20), pp. 14930-14941. Date of Electronic Publication: 2021 Oct 12.
DOI: 10.1021/acs.jmedchem.1c01067
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: