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proTAME is a cell-permeable prodrug form of N-4-tosyl-L-arginine methyl ester , an inhibitor of the anaphase-promoting complex/cyclosome (APC/C), that is converted to TAME by intracellular esterases. proTAME (12 μM) blocks association of APC/C with the activator CDH1 and inhibits degradation of APC/C substrates in HeLa cells. It induces mitotic arrest in metaphase followed by cell death in synchronized HeLa H2B-GFP cells when used at a concentration of 12 μM. It also increases mitotic duration in asynchronous HeLa H2B-GFP cells at a concentration of 4 μM, an effect that is enhanced by knockdown of the APC/C co-activator CDC20. proTAME decreases the viability of several laboratory and primary patient-derived human multiple myeloma (MM) cell lines (IC50s = 2.8-20.3 μM) and increases apoptosis in RPMI-8226, LP-1, NCI-H929, and U266 MM cells when used at a concentration of 12 μM.

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