Activation of RyR2 by class I kinase inhibitors

Kinase inhibitors are a common treatment for cancer. Class I kinase inhibitors that target the ATP-binding pocket are particularly prevalent. Many of these compounds are cardiotoxic and can cause arrhythmias. Spontaneous release of Ca2+ via cardiac ryanodine receptors (RyR2), through a process terme...

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Autores principales: Chakraborty, A. D., Gonano, Luis Alberto, Munro, M. L., Smith, L. J, Thekkedam, C., Staudacher, V., Gamble, A. B., Macquaide, N., Dulhunty, A. F., Jones, P. P.
Formato: Articulo
Lenguaje:Español
Publicado: 2019
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/108114
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6393232&blobtype=pdf
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Sumario:Kinase inhibitors are a common treatment for cancer. Class I kinase inhibitors that target the ATP-binding pocket are particularly prevalent. Many of these compounds are cardiotoxic and can cause arrhythmias. Spontaneous release of Ca2+ via cardiac ryanodine receptors (RyR2), through a process termed store overload-induced Ca2+ release (SOICR), is a common mechanism underlying arrhythmia. We explored whether class I kinase inhibitors could modify the activity of RyR2 and trigger SOICR to determine if this contributes to the cardiotoxic nature of these compounds.