Apcin Licensed from Randy King Lab at Harvard

Boston Biochem and Professor Randy King are again partnering on a breakthrough product for ubiquitin research.  Apcin is a cell-permeable compound capable of slowing APC-dependent proteolysis.  


Apcin functions by inhibiting substrate binding to Cdc20, the mitotic activator of the ubiquitin ligase activity of the anaphase-promoting complex/cyclosome (APC/C).  The mechanism of action is distinct from that of another APC/C inhibitor, proTAME (I-440), which binds APC/C and inhibits both Cdc20- and Cdh1-dependent proteolysis.  


When used alone in cultured cells, apcin blocks mitotic exit only modestly. (concentrations of 50-100 ┬ÁM are required to slow mitotic exit).  However, a strong synergistic effect is observed when apcin and proTAME are used simultaneously.  Co-administration of the compounds provides a more robust mitotic arrest than would be predicted by additive models.  This may be very beneficial when treating cells that do not efficiently convert proTAME to its active parent compound (TAME, tosyl-L-arginine methyl ester), or if experiments demand strong APC/C inhibition.