posted on 2021-10-12, 12:07authored byScott E. Collibee, Gustave Bergnes, Chihyuan Chuang, Luke Ashcraft, Jeffrey Gardina, Marc Garard, Chris R. Jamison, Kevin Lu, Pu-Ping Lu, Alexander Muci, Antonio Romero, Ellen Valkevich, Wenyue Wang, Jeffrey Warrington, Bing Yao, Nickie Durham, James Hartman, Anna Marquez, Aaron Hinken, Julia Schaletzky, Donghong Xu, Darren T. Hwee, David Morgans, Fady I. Malik, Bradley P. Morgan
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.