Marizomib

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206763

CAS#: 437742-34-2

Description: Marizomib, also known as ML 858, NPI-0052 and Salinosporamide A, is a potent and selective 20S proteasome inhibitor from natural origin. Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients. Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. Marizomib exhibits prolonged inhibition, attenuated efflux, and greater cytotoxicity than its reversible analogs.


Price and Availability

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Marizomib is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206763
Name: Marizomib
CAS#: 437742-34-2
Chemical Formula: C15H20ClNO4
Exact Mass: 313.1081
Molecular Weight: 313.778
Elemental Analysis: C, 57.42; H, 6.42; Cl, 11.30; N, 4.46; O, 20.40


Synonym: ML 858; ML-858; ML858; NPI 0052; NPI-0052; NPI0052; Marizomib; (-)-Salinosporamide A; Salinosporamide A.

IUPAC/Chemical Name: (1R,4R,5S)-4-(2-chloroethyl)-1-((S)-((S)-cyclohex-2-en-1-yl)(hydroxy)methyl)-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione

InChi Key: NGWSFRIPKNWYAO-SHTIJGAHSA-N

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

SMILES Code: C[C@]12[C@H](C(=O)N[C@]1(C(=O)O2)[C@H]([C@H]3CCCC=C3)O)CCCl


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Levin N, Spencer A, Harrison SJ, Chauhan D, Burrows FJ, Anderson KC, Reich SD, Richardson PG, Trikha M. Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients. Br J Haematol. 2016 Sep;174(5):711-20. doi: 10.1111/bjh.14113. PubMed PMID: 27161872; PubMed Central PMCID: PMC5084787.

2: Harrison SJ, Mainwaring P, Price T, Millward MJ, Padrik P, Underhill CR, Cannell PK, Reich SD, Trikha M, Spencer A. Phase I Clinical Trial of Marizomib (NPI-0052) in Patients with Advanced Malignancies Including Multiple Myeloma: Study NPI-0052-102 Final Results. Clin Cancer Res. 2016 Sep 15;22(18):4559-66. doi: 10.1158/1078-0432.CCR-15-2616. PubMed PMID: 27117181.

3: Richardson PG, Zimmerman TM, Hofmeister CC, Talpaz M, Chanan-Khan AA, Kaufman JL, Laubach JP, Chauhan D, Jakubowiak AJ, Reich S, Trikha M, Anderson KC. Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma: NPI-0052-101 Part 1. Blood. 2016 Jun 2;127(22):2693-700. doi: 10.1182/blood-2015-12-686378. PubMed PMID: 27009059.

4: Manton CA, Johnson B, Singh M, Bailey CP, Bouchier-Hayes L, Chandra J. Induction of cell death by the novel proteasome inhibitor marizomib in glioblastoma in vitro and in vivo. Sci Rep. 2016 Jan 25;6:18953. doi: 10.1038/srep18953. PubMed PMID: 26804704; PubMed Central PMCID: PMC4726202.

5: Di K, Lloyd GK, Abraham V, MacLaren A, Burrows FJ, Desjardins A, Trikha M, Bota DA. Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. Neuro Oncol. 2016 Jun;18(6):840-8. doi: 10.1093/neuonc/nov299. PubMed PMID: 26681765; PubMed Central PMCID: PMC4864261.

6: Das DS, Ray A, Song Y, Richardson P, Trikha M, Chauhan D, Anderson KC. Synergistic anti-myeloma activity of the proteasome inhibitor marizomib and the IMiD immunomodulatory drug pomalidomide. Br J Haematol. 2015 Dec;171(5):798-812. doi: 10.1111/bjh.13780. PubMed PMID: 26456076; PubMed Central PMCID: PMC4715649.

7: Corrales-Medina FF, Manton CA, Orlowski RZ, Chandra J. Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models. Leuk Res. 2015 Mar;39(3):371-9. doi: 10.1016/j.leukres.2014.12.014. PubMed PMID: 25612941; PubMed Central PMCID: PMC4420632.

8: Ma L, Diao A. Marizomib, a potent second generation proteasome inhibitor from natural origin. Anticancer Agents Med Chem. 2015;15(3):298-306. Review. PubMed PMID: 25403165.

9: Niewerth D, Jansen G, Riethoff LF, van Meerloo J, Kale AJ, Moore BS, Assaraf YG, Anderl JL, Zweegman S, Kaspers GJ, Cloos J. Antileukemic activity and mechanism of drug resistance to the marine Salinispora tropica proteasome inhibitor salinosporamide A (Marizomib). Mol Pharmacol. 2014 Jul;86(1):12-9. doi: 10.1124/mol.114.092114. PubMed PMID: 24737138; PubMed Central PMCID: PMC4054006.

10: Millward M, Price T, Townsend A, Sweeney C, Spencer A, Sukumaran S, Longenecker A, Lee L, Lay A, Sharma G, Gemmill RM, Drabkin HA, Lloyd GK, Neuteboom ST, McConkey DJ, Palladino MA, Spear MA. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Invest New Drugs. 2012 Dec;30(6):2303-17. doi: 10.1007/s10637-011-9766-6. PubMed PMID: 22080430.

11: Miller CP, Manton CA, Hale R, Debose L, Macherla VR, Potts BC, Palladino MA, Chandra J. Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs. Chem Biol Interact. 2011 Oct 15;194(1):58-68. doi: 10.1016/j.cbi.2011.08.005. PubMed PMID: 21864512; PubMed Central PMCID: PMC3186881.

12: Obaidat A, Weiss J, Wahlgren B, Manam RR, Macherla VR, McArthur K, Chao TH, Palladino MA, Lloyd GK, Potts BC, Enna SJ, Neuteboom ST, Hagenbuch B. Proteasome regulator marizomib (NPI-0052) exhibits prolonged inhibition, attenuated efflux, and greater cytotoxicity than its reversible analogs. J Pharmacol Exp Ther. 2011 May;337(2):479-86. doi: 10.1124/jpet.110.177824. PubMed PMID: 21303921; PubMed Central PMCID: PMC3083100.

13: Potts BC, Albitar MX, Anderson KC, Baritaki S, Berkers C, Bonavida B, Chandra J, Chauhan D, Cusack JC Jr, Fenical W, Ghobrial IM, Groll M, Jensen PR, Lam KS, Lloyd GK, McBride W, McConkey DJ, Miller CP, Neuteboom ST, Oki Y, Ovaa H, Pajonk F, Richardson PG, Roccaro AM, Sloss CM, Spear MA, Valashi E, Younes A, Palladino MA. Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011 Mar;11(3):254-84. Review. PubMed PMID: 21247382; PubMed Central PMCID: PMC3712795.

14: Potts BC, Lam KS. Generating a generation of proteasome inhibitors: from microbial fermentation to total synthesis of salinosporamide a (marizomib) and other salinosporamides. Mar Drugs. 2010 Mar 25;8(4):835-80. doi: 10.3390/md8040835. Review. PubMed PMID: 20479958; PubMed Central PMCID: PMC2866466.

15: Ling T, Potts BC, Macherla VR. Concise formal synthesis of (-)-salinosporamide A (marizomib) using a regio- and stereoselective epoxidation and reductive oxirane ring-opening strategy. J Org Chem. 2010 Jun 4;75(11):3882-5. doi: 10.1021/jo100432g. PubMed PMID: 20465296.

16: Singh AV, Palladino MA, Lloyd GK, Potts BC, Chauhan D, Anderson KC. 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. doi: 10.1111/j.1365-2141.2010.08144.x. PubMed PMID: 20331453; PubMed Central PMCID: PMC4427841.