RADIOACTIVELY LABELED 1,4-BENZOTHIAZEPINES AND METHODS OF SCREENING FOR COMPOUNDS THAT BIND RYANODINE RECEPTORS

摘要

The present invention provides certain radioactively labeled 1,4-benzothiazepine compounds that are useful in methods of screening for candidate compounds that bind a ryanodine receptor (RyR). The compounds are defined by structural formulae and the screening method includes the steps of incubating the RyR with a candidate compound in the presence or absence of a radioactively labeled compound so as to prepare a competitively bound-RyR composition containing RyR-bound candidate compound, RyR-bound radioactively labeled compound, or a combination thereof; separating the RyR-bound composition from un-bound radioactively labeled compound; measuring the radioactivity of the competitively RyR-bound composition; and determining whether the candidate compound binds the RyR based on the proportion of RyR-bound radioactively labeled compound in the presence and absence of the candidate compound.