{"id":9785,"date":"2024-04-12T10:12:53","date_gmt":"2024-04-12T10:12:53","guid":{"rendered":"https:\/\/www.caltagmedsystems.co.uk\/information\/?p=9785"},"modified":"2025-04-17T13:19:19","modified_gmt":"2025-04-17T13:19:19","slug":"salinosporamide-a-marizomib-potent-proteasome-inhibitor","status":"publish","type":"post","link":"https:\/\/www.caltagmedsystems.co.uk\/information\/salinosporamide-a-marizomib-potent-proteasome-inhibitor\/","title":{"rendered":"Salinosporamide A [Marizomib] – Potent Proteasome Inhibitor"},"content":{"rendered":"\n
\"\"<\/a>
Figure:<\/strong> The Ubiquitin-Proteasome System Inhibition and affected Cellular Processes<\/figcaption><\/figure>\n\n\n\n

The 26S proteasome complex recognises polyubiquitinated proteins, which were marked for elimination by the E1, E2 and E3 ubiquitinating enzymes (see Figure). Upon recognition, unfolding and transfer of the de-ubiquitinated target protein by the 19S regulatory cap into the interior of the cylindrical 20S proteasome core particle, protein degradation is facilitated by catalytic \u03b2-subunits having nucleophilic N-terminal threonine (Thr1) residues. Although eukaryotic 20S proteasomes harbour seven different \u03b2-subunits in their two-fold symmetrical \u03b17\u03b27\u03b27\u03b17 stacked complexes, only three \u03b2-subunits per \u03b2-ring [subunits \u03b21 (caspase-like), \u03b22 (trypsin-like) and \u03b25 (chymotrypsin-like)] are proteolytically active. These three \u03b2-subunits are major targets for small-molecule proteasome inhibitors.<\/p>\n\n\n\n

Salinosporamide A is a novel, second-generation irreversible pan-proteasome inhibitor, characterised by a unique \u03b2-lactone \u03b3-lactam bicyclic ring structure. It inhibits the 3 constitutive activities of the mammalian 20S proteasome (chymotrypsin-like, \u03b25 [CT-L]); trypsin-like, \u03b22 [T-L] and caspase-like, \u03b21 [C-L]). Salinosporamide A is effective at nanomolar concentrations in vitro and demonstrates penetration in vivo into multiple different organs including the CNS, crossing the blood-brain barrier (BBB). Non-clinical studies have demonstrated that salinosporamide A rapidly forms a covalent chemical bond at the active enzymatic sites (\u03b25, \u03b22 and \u03b21) in the proteasome resulting in irreversible inhibition at nanomolar concentrations. Extensive preclinical studies demonstrate the activity of salinosporamide A in a wide variety of hematopoietic, solid and CNS tumour models. Because of the enhanced CNS penetrating capability of salinosporamide A, given its lipophilic structure, it is especially of interest as a reagent in CNS tumour research.<\/p>\n\n\n\n

Literature References:<\/h4>\n\n\n\n
    \n
  1. Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora: R.H. Feling, et al.; Angew. Chem. Int. Ed. Engl. 42,<\/strong> 355 (2003)<\/li>\n\n\n\n
  2. Discovery and development of the anticancer agent salinosporamide A (NPI-0052): W. Fenical, et al.; Bioorg. Med. Chem. 17,<\/strong> 2175 (2009)<\/li>\n\n\n\n
  3. Generating a generation of proteasome inhibitors: from microbial fermentation to total synthesis of salinosporamide a (marizomib) and other salinosporamides: B.C. Potts & K.S. Lam; Mar. Drugs 8,<\/strong> 835 (2010) (Review)<\/li>\n\n\n\n
  4. Salinosporamide natural products: Potent 20S proteasome inhibitors as promising cancer chemotherapeutics: T.A. Gulder & B.S. Moore; Angew. Chem. Int. Ed. Engl. 49,<\/strong> 9346 (2010) (Review)<\/li>\n\n\n\n
  5. Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials: B.C. Potts, et al.; Curr. Cancer Drug Targets 11,<\/strong> 254 (2011)<\/li>\n\n\n\n
  6. Proteasome Inhibition in Multiple Myeloma: Head-to-Head Comparison of Currently Available Proteasome Inhibitors: A. Besse, et al.; Cell Chem. Biol. 26,<\/strong> 340 (2019)<\/li>\n<\/ol>\n\n\n\n

    Salinosporamide A<\/h2>\n\n\n\n

    Salinosporamide A is a potent, irreversible inhibitor of all the 3 proteolytic activities of the mammalian 20S proteasome. \u03b25 subunit: chymotrypsin-like (EC50 = 3.5nM); \u03b22 subunit: trypsin-like (EC50 = 28nM); \u03b21 subunit: caspase-like or peptidyl-glutamyl peptide-hydrolyzing (PGPH) (EC50 = 430nM). Salinosporamide A is a potent anticancer compound. It triggers apoptosis with distinct proteasome activity and mechanism of action compared to bortezomib (Velcade) (Prod. No. AG-CR1-3602). It displays a longer inhibition duration than bortezomib and shows potent antileukemic activity against bortezomib-resistant leukaemia cells.<\/p>\n\n\n\n

    AG-CN2-0444<\/a> (100\u00b5g, 1 mg, 5 mg, 50 mg and BULK) <\/p>\n\n\n\n

    AdipoGen Life Sciences is an original Manufacturer of high-purity Salinosporamide A. BULK quantities are available from Stock!<\/p>\n\n\n\n

    \n

    Product Specifications:<\/h4>\n\n\n\n

    CAS<\/strong>:        437742-34-2
    Source<\/strong>:   Isolated from Salinospora tropical <\/em>(Marine)
    Purity<\/strong>:     >98% HPLC
    Identity<\/strong>:  Determined by 1<\/sup>H-NMR<\/p>\n<\/div>

    \"\"<\/figure><\/div>\n\n\n\n
    \n
    Read About Salinosporamide on Adipogen’s Website<\/strong><\/a><\/div>\n\n\n\n
    View Flyers on Small Molecules<\/strong><\/a><\/div>\n<\/div>\n\n\n\n
    \n\n\n\n

    Originally posted by Adipogen on: https:\/\/adipogen.com\/salinosporamide<\/a><\/p>\n\n\n\n

    Caltag Medsystems <\/a>is the distributor of Adipogen<\/a> products in the UK and Ireland. If you have any questions about these products, please contact<\/a> us<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

    AdipoGen is a manufacturer of Salinosporamide A – a potent, irreversible inhibitor of all 3 proteolytic activities of the mammalian 20S proteasome.<\/p>\n","protected":false},"author":13,"featured_media":8072,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,681],"tags":[279,846,49],"class_list":["post-9785","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-general-information","category-proteins","tag-adipogen","tag-salinosporamide","tag-ubiquitin"],"_links":{"self":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/9785","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/comments?post=9785"}],"version-history":[{"count":4,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/9785\/revisions"}],"predecessor-version":[{"id":12140,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/9785\/revisions\/12140"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/media\/8072"}],"wp:attachment":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/media?parent=9785"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/categories?post=9785"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/tags?post=9785"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}