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Purity: ≥98%
Marizomib (formerly also known as ML-858, NPI-0052 and Salinosporamide A), a naturally occurring salinosporamide with potential antineoplastic activity has been isolated from the marine actinomycete Salinospora tropica. It is a strong and selective inhibitor of the 20S proteasome (IC50 = 1.3 nM). Marizomib prevents compensatory hyperactivation in patients with solid tumors and multiple myeloma by irreversibly inhibiting the proteasome. Marizomib's capacity to cross the blood-brain barrier is its sole therapeutic action in malignant gliomas. Compared to its reversible analogs, marizomib shows longer inhibition, reduced efflux, and increased cytotoxicity.
| Targets |
CT-L (IC50 = 3.5 nM); CT-T-laspase-like (IC50 = 28 nM); trypsin-like (IC50 = 430 nM)
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|---|---|
| ln Vitro |
Marizomib (Salinosporamide A) (0.1-10000 nM; 72 hours) effectively and dose-dependently decreases D-54 and U-251 cell survival. For D-54 and U-251, the IC50s are ≤20 nM and ～52 nM, respectively[1].
Marizomib (24 hours; 60 nM) causes apoptosis and caspase-3 activation in glioma cells[1]. |
| ln Vivo |
Marizomib (Salinosporamide A) (0.15 mg/kg; i.v; twice a week for three weeks) is associated with no toxicity and significantly reduces the growth of tumors[3].
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| Cell Assay |
Proteasome activity is assessed in neural stem cells and glioblastoma-derived glioma stem cells at baseline and two hours following marizomib (60 nM) treatment. Using Matrigel invasion chambers, the invading potential of D-54 MG and U-251 MG cells treated or not treated with 60 nM marizomib for a 24-hour period is examined.
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| Animal Protocol |
CB-17 SCID-male mice (4-6 weeks old)[3]
0.15 mg/kg i.v; twice a week for three weeks |
| References |
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| Additional Infomation |
Salinosporamide A is a salinosporamide in which the core (1R)-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione skeleton is substituted at positions 1, 4, and 5 by (1S)-cyclohex-2-en-1-yl(hydroxy)methyl, 2-chloroethyl, and methyl groups, respectively (the 1R,4R,5S diastereoisomer). A potent proteasome inhibitor, it has attracted interest for potential use in the treatment of various cancers. It has a role as an antineoplastic agent and a proteasome inhibitor. It is a salinosporamide, an organochlorine compound, an organic heterobicyclic compound, a beta-lactone and a gamma-lactam.
Marizomib has been used in trials studying the treatment of Cancer, Melanoma, Lymphoma, Glioblastoma, and Malignant Glioma, among others. Marizomib has been reported in Salinispora and Salinispora tropica with data available. Marizomib is a naturally-occurring salinosporamide, isolated from the marine actinomycete Salinospora tropica, with potential antineoplastic activity. Marizomib irreversibly binds to and inhibits the 20S catalytic core subunit of the proteasome by covalently modifying its active site threonine residues; inhibition of ubiquitin-proteasome mediated proteolysis results in an accumulation of poly-ubiquitinated proteins, which may result in the disruption of cellular processes, cell cycle arrest, the induction of apoptosis, and the inhibition of tumor growth and angiogenesis. This agent more may more potent and selective than the proteasome inhibitor bortezomib. Drug Indication Treatment of malignant glial tumours |
| Molecular Formula |
C15H20CLNO4
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|---|---|
| Molecular Weight |
313.7766
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| Exact Mass |
313.108
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| Elemental Analysis |
C, 57.42; H, 6.42; Cl, 11.30; N, 4.46; O, 20.40
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| CAS # |
437742-34-2
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| Related CAS # |
437742-34-2
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| PubChem CID |
11347535
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| Appearance |
Off-white to pink solid powder
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| LogP |
1.408
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
508
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O=C([C@H](CCCl)[C@]1(C)O2)N[C@@]1([C@H]([C@@H]3C=CCCC3)O)C2=O
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| InChi Key |
NGWSFRIPKNWYAO-SHTIJGAHSA-N
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| InChi Code |
InChI=1S/C15H20ClNO4/c1-14-10(7-8-16)12(19)17-15(14,13(20)21-14)11(18)9-5-3-2-4-6-9/h3,5,9-11,18H,2,4,6-8H2,1H3,(H,17,19)/t9-,10+,11+,14+,15+/m1/s1
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| Chemical Name |
(1R,4R,5S)-4-(2-chloroethyl)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione
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| Synonyms |
ML 858; NPI0052; Marizomib; ML-858; NPI-0052; (-)-Salinosporamide A; ML858; NPI 0052; Salinosporamide A
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (~318.7 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1869 mL | 15.9347 mL | 31.8695 mL | |
| 5 mM | 0.6374 mL | 3.1869 mL | 6.3739 mL | |
| 10 mM | 0.3187 mL | 1.5935 mL | 3.1869 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04341311 | Active Recruiting |
Drug: Marizomib Drug: Panobinostat |
Pediatric Cancer Diffuse Glioma |
Dana-Farber Cancer Institute | August 10, 2020 | Phase 1 |
| NCT05050305 | Not yet recruiting | Drug: Marizomib Drug: Pomalidomide |
Multiple Myeloma Multiple Myeloma in Relapse |
Dana-Farber Cancer Institute | March 2024 | Phase 2 |
| NCT03345095 | Active Recruiting |
Drug: Marizomib Drug: Temozolomide |
Newly Diagnosed Glioblastoma | European Organisation for Research and Treatment of Cancer - EORTC |
July 26, 2018 | Phase 3 |
| NCT00396864 | Completed | Drug: NPI-0052 | Cancer Lymphomas |
Celgene | May 2006 | Phase 1 |
| NCT00461045 | Completed | Drug: MRZ 0.5 mg/m^2 | Multiple Myeloma | Celgene | March 2007 | Phase 2 |
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