The present invention provides novel 1,4-benzothiazepine intermediates and
derivatives, methods for synthesizing same, and methods for assaying
same. The present invention also provides methods for using these novel
compounds to limit or prevent a decrease in the level of RyR2-bound
FKBP12.6 in a subject; to prevent exercise-induced sudden cardiac death
in a subject; and to treat or prevent heart failure, atrial fibrillation,
or exercise-induced cardiac arrhythmia in a subject. The present
invention further provides methods for identifying an agent that enhances
binding of RyR2 and FKBP12.6, and agents identified by these methods.
Additionally, the present invention provides methods for identifying
agents for use in treating or preventing heart failure, atrial
fibrillation, or exercise-induced cardiac arrhythmia, and in preventing
exercise-induced sudden cardiac death. Also provided are agents
identified by such methods.