Rapaprotin is a selective apoptosis inducer in multiple myeloma cells (NCI-H929, IC50=156 nM) and 26S proteasome assembly inhibitor.
Rapaprotin also less potently inhibits cell viability of other MM and hematopoietic cancer cell lines.
Rapaprotin induces apoptosis through activation of caspases in MM cells, induces the cleavage of procaspases-3, -7 and -8 in a dose-dependent manner, causes significant cleavage of pro-caspase-3 in NCI-H929 and to a lesser degree in Jurkat T cells.
Rapaprotin also induces PARP cleavage in a dose- and time-dependent manner in NCI-H929 cells
Papaprotin is activated by prolyl endopeptidase (PREP) in MM cells.
Rapaprotin inhibits the ubiquitin-proteasome pathway, inhibits proteasome activity in FZ120-H929 cells with IC50 of 817 nM, induces unfolded-protein response (UPR) in NCI-H929 cells, its activated form, rapaprotin-L, inhibits proteasome activity in vitro.
Rapaprotin-L is potent against the trypsin-(IC50 = 4.9 µM) and chymotrypsin-like (IC50 = 8.6 µM) activities than the caspase-like activity (IC50 = 17.6 µM), but not the cyclic rapaprotin.
Rapaprotin-L induces 26S proteasome disassembly.
Rapaprotin synergizes with bortezomib and re-sensitizes bortezomib-resistant MM cells.