Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator.

Abstract:

:The identification and optimization of the first activators of fast skeletal muscle are reported. Compound 1 was identified from high-throughput screening (HTS) and subsequently found to improve muscle function via interaction with the troponin complex. Optimization of 1 for potency, metabolic stability, and physical properties led to the discovery of tirasemtiv (25), which has been extensively characterized in clinical trials for the treatment of amyotrophic lateral sclerosis.

journal_name

ACS Med Chem Lett

authors

Collibee SE,Bergnes G,Muci A,Browne WF 4th,Garard M,Hinken AC,Russell AJ,Suehiro I,Hartman J,Kawas R,Lu PP,Lee KH,Marquez D,Tomlinson M,Xu D,Kennedy A,Hwee D,Schaletzky J,Leung K,Malik FI,Morgans DJ Jr,Morgan BP

doi

10.1021/acsmedchemlett.7b00546

subject

Has Abstract

pub_date

2018-02-13 00:00:00

pages

354-358

issue

4

issn

1948-5875

journal_volume

9

pub_type

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