1. Activation of RyR2 by class I kinase inhibitors
- Author
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Chakraborty, A. D., Gonano, Luis Alberto, Munro, M. L., Smith, L. J, Thekkedam, C., Staudacher, V., Gamble, A. B., Macquaide, N., Dulhunty, A. F., and Jones, P. P.
- Subjects
ATP ,Ciencias Médicas ,Sunitinib ,cardiovascular system ,RyR2 ,purl.org/becyt/ford/3 [https] ,purl.org/becyt/ford/3.1 [https] ,Nilotinib - Abstract
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., Centro de Investigaciones Cardiovasculares
- Published
- 2019