Marizomib
CAS No. : 437742-34-2

Marizomib
Cat. No. : CS-0002986
M. Wt. : 313.78
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  • Data Sheet

  • Introduction

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Name: Marizomib; (-)-Salinosporamide A;  ML 858;  NPI 0052
Cat. No. : CS-0002986
CAS No. : 437742-34-2
Formula: C15H20ClNO4
M. Wt. : 313.78
Solubility: DMSO

Activity:

Marizomib is a second-generation, irreversible proteasome inhibitor. IC50 & Target: Target: Proteasome[1] In Vitro: Marizomib has a broader inhibition profile for the 20S proteasome compared with bortezomib and carfilzomib and has been shown to inhibit the CT-L (β5) CT-T-laspase-like (C-L, β1) and trypsin-like (T-L, β2) activities of the 20S proteasome. Marizomib inhibits the proteasome activity, proliferation, and invasion of glioma cells. Meanwhile, free radical production and apoptosis induced by Marizomib could be blocked by antioxidant N-acetyl cysteine[1]. In Vivo: Marizomib distributes into the brain at 30% of blood levels in rats and significantly inhibits (>30%) baseline chymotrypsin-like proteasome activity in brain tissue of monkeys. The immunocompromised mice, intracranially implanted with glioma xenografts, survive significantly longer than the control animals (P< .05) when treated with Marizomib[1].

Protocol:

Cell Assay: [1]D-54 cells are treated with either 20 nM or 60 nM of Marizomib for 24 hours. The apoptotic cells are measured using the Annexin V:FITC Apoptosis Detection kit[1]. Animal Administration: Marizomib is prepared in 2% DMSO in 5% Solutol.[1]Mice[1]

Five groups of 6-8 week old mice (n=3 mice per group) are treated with either control vehicle (2% DMSO in 5% Solutol) or different doses of Marizomib (150, 200, 250, and 300 µg/kg). The drug is administered biweekly for 2.5 weeks (on days 1, 4, 8, 11, and 15) into the tail vein of the animals, and the animals are monitored for survival. The maximum tolerated dose (MTD) of Marizomib is determined to be 200 µg/kg[1].

References:

Di K, et al. Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. Neuro Oncol. 2016 Jun;18(6):840-8.

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