Marizomib is a novel irreversible brain-permeable proteasome inhibitor that inhibits CT-L (β5), CT-T-laspase-like (C-L, β1), and trypsin-like (T-L, β2) 20S proteasomes with IC50s of 3.5, 28, and 430 nM.[3]

Trypsin like:430 nM, CTL laspase-like:28 nM, CTL:3.5 nM

METHODS: TNBC (basal), ductal and non-malignant breast epithelial cells were treated with Marizomib (0-500 nM) and cell proliferation was analyzed using the MTS assay after 6 days.
RESULTS Marizomib selectively reduced TNBC cell proliferation in a concentration-dependent manner without much effect on non-TNBC and non-malignant mammary epithelial cells (MCF10A and D492), with IC50 values of Marizomib less than 150 nM in TNBC cell lines and greater than 1 µM in non-TNBC cell lines.[1]
METHODS: SUM159PT cells were treated with 100 nM Marizomib for 0 and 9 hours (prior to induction of apoptosis) and label-free global proteomics analysis was performed to identify proteins or pathways altered by Marizomib.
RESULTS A total of 2547 proteins were identified, of which 425 proteins were downregulated (log2 ≤ 0.6) and 293 proteins were upregulated (log2 ≥ 0.6).Marizomib decreased the levels of 11 proteasome subunits, and 5 proteasome subunits (PSMA5, PSMC2, PSMD2, PSMA1, PSMA7 and PSMA8) were also observed to be Up-regulation. [1]
METHODS: Cells were treated with 40 nM or 80 nM marizomib for 4 h. CT-L activity of proteasome in total cell lysates was determined by lysing Suc-LLVY-AMC.
RESULTS marizomib effectively inhibited proteasomes in both responsive and non-responsive cells. [2]

METHODS: After two weeks of Marizomib (0.15 mg/kg twice/week, IP) treatment of MDA-MB-231 xenografts and patient-derived tumor xenografts (PDX), it was observed whether tumor growth was inhibited in vivo.
RESULTS Marizomib treatment significantly reduced tumor volume and tumor weight in MDA-MB-231 xenografts and patient-derived tumor xenografts (PDX). [1]