Macrolide analogs and methods for identifying macrolide analogs capable of
unregulated inhibition of actin filament dynamics are provided. A method
according to the invention includes the steps of: (a) contacting F-actin
with a candidate compound; and (b) assaying the candidate compound's
ability to sever the F-actin and cap resulting F-actin (+)-ends. The
candidate compound is identified as a macrolide analog where said
candidate compound displays an ability to sever F-actin and, following
severing, the resulting F-actin (+)-end is capped by the candidate
compound thusly preventing subsequent G-actin incorporation. Severing and
capping activities are unregulated; i.e., independent of at least
physiologically-meaningful concentrations of phosphatidyl inositol and
calcium.