Marizomib

Cas No.:	437742-34-2
Chemical Name:	(1R,4R,5S)-4-(2-Chloroethyl)-1-[(S)-(1S)-2-cyclohexen-1-ylhydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione
Synonyms:	NPI 0052;Salinosporamide A
SMILES:	ClCC[C@H]1C(=O)N[C@]2(C(O[C@@]12C)=O)[C@H]([C@H]1CCCC=C1)O
Formula:	C15H20ClNO4
M.Wt:	313.781
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Marizomib (Salinosporamide A) is second-generation, irreversible, brain-penetrant, pan-proteasome inhibitor. Marizomib inhibits the CT-L (β5), CT-T-laspase-like (C-L, β1) and trypsin-like (T-L, β2) activities of the 20S proteasome (IC50=3.5, 28, and 430 nM, respectively)[1][2][3].
Target:	IC50: 3.5 nM (CT-L), 28 nM (CT-T-laspase-like), 430 nM (trypsin-like)[1]
In Vivo:	Marizomib (Salinosporamide A) (0.15 mg/kg; i.v; twice a week for three weeks) significantly decreases tumor growth, and is not associated with any toxicity[3]. Animal Model: CB-17 SCID-male mice (4-6 weeks old)[3] Dosage: 0.15 mg/kg Administration: i.v; twice a week for three weeks Result: Significantly decreased tumor growth, and was not associated with any toxicity.
In Vitro:	Marizomib (Salinosporamide A) (0.1-10000 nM; 72 hours) effectively reduces survival of D-54 and U-251 cells in a dose-dependent manner. The IC50s are ∼52 nM for U-251 and ∼20 nM for D-54[1]. Marizomib (24 hours; 60 nM) induces apoptosis and caspase-3 activation in glioma cells[1]. Cell Proliferation Assay[1] Cell Line: U-251 and D-54 cells Concentration: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Time: 72 hours Result: Effectively reduced survival of D-54 and U-251 cells in a dose-dependent manner. Apoptosis Analysis[1] Cell Line: D-54 cells Concentration: 60 nM Incubation Time: 24 hours Result: Induces D-54 cells apoptosis. Western Blot Analysis[1] Cell Line: D-54 cells Concentration: 60 nM Incubation Time: 24 hours Result: Led to increased activity of caspase-3 in a dose-dependent manner.
References:	[1]. Di K, et al. Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brainbarrier. Neuro Oncol. 2016 Jun;18(6):840-8. [2]. Kale AJ, et al. Molecular mechanisms of acquired proteasome inhibitor resistance. J Med Chem. 2012 Dec 13;55(23):10317-27. [3]. Singh AV, et al. Pharmacodynamic and efficacy studies of the novel proteasome inhibitor NPI-0052 (marizomib) in a human plasmacytoma xenograft murine model. Br J Haematol. 2010 May;149(4):550-9.