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

[Image: see text] 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 potenc...

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Autores principales: Collibee, Scott E., Bergnes, Gustave, Muci, Alexander, Browne, William F., Garard, Marc, Hinken, Aaron C., Russell, Alan J., Suehiro, Ion, Hartman, James, Kawas, Raja, Lu, Pu-Ping, Lee, Kenneth H., Marquez, David, Tomlinson, Matthew, Xu, Donghong, Kennedy, Adam, Hwee, Darren, Schaletzky, Julia, Leung, Kwan, Malik, Fady I., Morgans, David J., Morgan, Bradley P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900333/
https://www.ncbi.nlm.nih.gov/pubmed/29670700
http://dx.doi.org/10.1021/acsmedchemlett.7b00546
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author Collibee, Scott E.
Bergnes, Gustave
Muci, Alexander
Browne, William F.
Garard, Marc
Hinken, Aaron C.
Russell, Alan J.
Suehiro, Ion
Hartman, James
Kawas, Raja
Lu, Pu-Ping
Lee, Kenneth H.
Marquez, David
Tomlinson, Matthew
Xu, Donghong
Kennedy, Adam
Hwee, Darren
Schaletzky, Julia
Leung, Kwan
Malik, Fady I.
Morgans, David J.
Morgan, Bradley P.
author_facet Collibee, Scott E.
Bergnes, Gustave
Muci, Alexander
Browne, William F.
Garard, Marc
Hinken, Aaron C.
Russell, Alan J.
Suehiro, Ion
Hartman, James
Kawas, Raja
Lu, Pu-Ping
Lee, Kenneth H.
Marquez, David
Tomlinson, Matthew
Xu, Donghong
Kennedy, Adam
Hwee, Darren
Schaletzky, Julia
Leung, Kwan
Malik, Fady I.
Morgans, David J.
Morgan, Bradley P.
author_sort Collibee, Scott E.
collection PubMed
description [Image: see text] 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.
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spelling pubmed-59003332018-04-18 Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator Collibee, Scott E. Bergnes, Gustave Muci, Alexander Browne, William F. Garard, Marc Hinken, Aaron C. Russell, Alan J. Suehiro, Ion Hartman, James Kawas, Raja Lu, Pu-Ping Lee, Kenneth H. Marquez, David Tomlinson, Matthew Xu, Donghong Kennedy, Adam Hwee, Darren Schaletzky, Julia Leung, Kwan Malik, Fady I. Morgans, David J. Morgan, Bradley P. ACS Med Chem Lett [Image: see text] 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. American Chemical Society 2018-02-13 /pmc/articles/PMC5900333/ /pubmed/29670700 http://dx.doi.org/10.1021/acsmedchemlett.7b00546 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Collibee, Scott E.
Bergnes, Gustave
Muci, Alexander
Browne, William F.
Garard, Marc
Hinken, Aaron C.
Russell, Alan J.
Suehiro, Ion
Hartman, James
Kawas, Raja
Lu, Pu-Ping
Lee, Kenneth H.
Marquez, David
Tomlinson, Matthew
Xu, Donghong
Kennedy, Adam
Hwee, Darren
Schaletzky, Julia
Leung, Kwan
Malik, Fady I.
Morgans, David J.
Morgan, Bradley P.
Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator
title Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator
title_full Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator
title_fullStr Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator
title_full_unstemmed Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator
title_short Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator
title_sort discovery of tirasemtiv, the first direct fast skeletal muscle troponin activator
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900333/
https://www.ncbi.nlm.nih.gov/pubmed/29670700
http://dx.doi.org/10.1021/acsmedchemlett.7b00546
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