PR-924

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的特异性免疫蛋白酶体 LMP7 亚基抑制剂，IC50 为 25 nM。

A potent, specific immunoproteasome LMP7 subunit inhibitor with IC50 of 25 nM, >100-fold selectivity over β5c, β1i, β1c, β2i and β2c subunits (IC50>3 uM); shows weak activity toward LMP2 and no detectable activity toward β1, β2, or MECL1.

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). PR-924 (3 μM; 48 hours; MM.1S and MM.1R cells) treatment triggers apoptosis in MM cells. 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. 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. Cell Viability AssayCell Line:MM.1S, MM.1R, RPMI-8226, KMS12, LR-5, DOX40, INA-6, OPM1 and OPM2 cells Concentration:1-20 μM Incubation Time:24 hours, 48 hours, and 72 hours Result:Significantly decreased 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).Apoptosis Analysis Cell Line:MM.1S and MM.1R cells Concentration:3 μM Incubation Time:48 hours Result:Triggered a significant increase in the Annexin V+/PI-apoptotic cell population.Western Blot Analysis Cell Line:MM.1S and MM.1R cells Concentration:3 μM Incubation Time:48 hours Result:Triggered activation of caspase-3, caspase-8 and caspase-9, and significantly down-regulated the expression of Bcl-2 protein.

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. PR-924 treatment significant reduces the shIL-6R levels in SCID-hu model. Treatment of tumour-bearing mice with PR-924, prolongs survival. Animal Model:CB-17 SCID-mice injected with MM.1S cells Dosage:6 mg/kg Administration:Intravenous injection; twice a week; for 21 days Result:Inhibited tumour growth in human plasmacytoma xenografts.

IPSI | PR 924 | PR924

Proteasome/Ubiquitin

Proteasome

Proteasome

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1416709-79-9

618.734

C37H38N4O5

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (80.81 mM)

C[C@H](C(N[C@H](C(N[C@H](C([C@]1(CO1)C)=O)Cc2ccccc2)=O)Cc(c[nH]3)c4c3cccc4)=O)NC(C5=C(c6c(C5)cccc6)C)=O

N-((R)-1-(((S)-3-(1H-indol-3-yl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)-3-methyl-1H-indene-2-carboxamide

(-20℃)

With Ice Pack

≥ 2 years