{"id":67,"date":"2024-03-10T12:25:03","date_gmt":"2024-03-10T12:25:03","guid":{"rendered":"https:\/\/glocentrica.usquaresolutions.com\/?page_id=67"},"modified":"2024-03-16T11:33:31","modified_gmt":"2024-03-16T11:33:31","slug":"glyoxalase-1-inhibitor-therapeutics-for-multidrug-resistant-tumors","status":"publish","type":"page","link":"https:\/\/pjthornalley.com\/index.php\/glyoxalase-1-inhibitor-therapeutics-for-multidrug-resistant-tumors\/","title":{"rendered":"Glyoxalase 1 inhibitor therapeutics for multidrug resistant tumors"},"content":{"rendered":"\n

Summary<\/strong><\/p>\n\n\n\n

Glycation of DNA and the spliceosome by methylglyoxal (MG) often contribute to the antiproliferative and apoptotic response of cancer chemotherapy. Glyoxalase 1 (Glo1) of the glyoxalase system has a major role in the metabolism of MG. High expression of Glo1 contributes to multidrug resistance by shielding the spliceosome from MG modification and decreasing survival in the chemotherapy – particularly in the treatment of breast cancer. High Glo1 expression is a negative survival factor in chemotherapy of breast cancer where adjunct therapy with a Glo1 inhibitor may improve treatment outcomes. Cell permeable Glo1 inhibitor prodrugs have been developed to induce severe dicarbonyl stress as a prospective treatment for cancer \u2013 particularly for high Glo1 expressing-related multidrug resistant tumors. The prototype Glo1 inhibitor is prodrug S-p-bromobenzylglutathione cyclopentyl diester (BBGD). It has antitumor activity in vitro and in tumor-bearing mice in vivo. In the National Cancer Institute human tumor cell line screen, BBGD was most active against the glioblastoma SNB-19 cell line. Recently, potent antitumor activity was found in glioblastoma multiforme tumor-bearing mice. BBGD has not yet been evaluated clinically. Adjunct chemotherapy with Glo1 inhibitor may improve treatment outcomes in cancer chemotherapy, particularly in breast cancer and glioblastoma multiforme.<\/p>\n\n\n\n

Summary scheme<\/strong><\/p>\n\n\n\n

\"A<\/p>\n\n\n\n

Delivery of glyoxalase 1 inhibitor, S-p-bromobenzylglutathione, into cells by diester modification. Abbreviations: BBG, S-p-bromobenzylglutathione; BBGD, S-p-bromobenzylglutathione cyclopentyl diester; and \u03b3-GT, \u03b3-glutamyl transferase.<\/p>\n\n\n\n

Principal publications<\/strong><\/p>\n\n\n\n

Thornalley, P.J., Wyatt, C., Davies, N., Edwards, L.G., Kang, Y., Ladan, M.J. and Double, J. (1996) Antitumour activity of S-p-bromobenzylglutathione cyclopentyl diester in vitro and in vivo. Inhibition of glyoxalase I and induction of apoptosis. Biochem. Pharmacol. 51, 1365-1372.<\/a><\/p>\n\n\n\n

Alhujaily, M., Abbas, H., Xue, M., de la Fuente, A., Rabbani, N. and Thornalley, P.J.\u00a0 (2021) Studies of glyoxalase 1-linked multidrug resistance reveal glycolysis-derived reactive metabolite, methylglyoxal, is a common contributor in cancer chemotherapy targeting the spliceosome. Frontiers in Oncol 11, 748698<\/a><\/p>\n\n\n\n

Rabbani, N. and Thornalley, P.J. (2022) Emerging glycation-based therapeutics \u2013 glyoxalase 1 inducers and glyoxalase 1 inhibitors. Internat J. Molec. Sci.\u00a023<\/em>, 2453.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Summary Glycation of DNA and the spliceosome by methylglyoxal (MG) often contribute to the antiproliferative and apoptotic response of cancer chemotherapy. Glyoxalase 1 (Glo1) of the glyoxalase system has a major role in the metabolism of MG. High expression of Glo1 contributes to multidrug resistance by shielding the spliceosome from MG modification and decreasing survival […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"templates\/template-full.php","meta":{"footnotes":""},"class_list":["post-67","page","type-page","status-publish","hentry","post"],"_links":{"self":[{"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/pages\/67","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/comments?post=67"}],"version-history":[{"count":6,"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/pages\/67\/revisions"}],"predecessor-version":[{"id":118,"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/pages\/67\/revisions\/118"}],"wp:attachment":[{"href":"https:\/\/pjthornalley.com\/index.php\/wp-json\/wp\/v2\/media?parent=67"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}