PR-924

PR-924 is a selective tripeptide epoxyketone immunoproteasome subunit LMP-7 inhibitor with an IC₅₀ of 22 nM. PR-924 covalently modifies proteasomal N-terminal threonine active sites. PR-924 inhibits growth and triggers apoptosis in multiple myeloma (MM) cells. PR-924 has antitumor activities^[1][2]. IC50 & Target: IC50: 22 nM (LMP7), 8.2 μM (LMP2)^[2] In Vitro: PR-924 (1-20 μM; 24-72 hours; MM.1S, MM.1R, RPMI-8226, KMS12, LR-5, DOX40, INA-6, OPM1 and OPM2 cells) treatment significantly decreases the viability of all the MM cell lines in a time-and dose-dependent manner (IC ₅₀ range for cell lines: 3-7 μM for 48 h)^[1].
PR-924 (3 μM; 48 hours; MM.1S and MM.1R cells) treatment triggers apoptosis in MM cells^[1].
PR-924 (3 μM; 48 hours; MM.1S and MM.1R cells) treatment triggers activation of caspase-3, caspase-8 and caspase-9, and significantly down-regulated the expression of Bcl-2 protein, without altering Bax or MCL-1 protein levels^[1].
PR-924 induces BID cleavage and its translocation to mitochondria, as well as cyto-c release BID, a proapoptotic BH-3 family protein, is linked to mitochondria-mediated apoptotic signaling pathways via cyto-c release^[1]. In Vivo: PR-924 (6 mg/kg; intravenous injection; twice a week; for 21 days; CB-17 SCID-mice) treatment significantly inhibits tumour growth in human plasmacytoma xenografts^[1].
PR-924 treatment significant reduces the shIL-6R levels in SCID-hu model. Treatment of tumour-bearing mice with PR-924, prolongs survival^[1].