{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Markatos C"],"funding":["Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call Research-Create-Innovate","NIDDK NIH HHS"],"pagination":["4127"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11397358"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(17)"],"pubmed_abstract":["The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7. The subsequent release of mitoxantrone leads to its intracellular accumulation, thus exerting its cytotoxic effects. To test this hypothesis, we determined the cytotoxic effects of Con-3 and Con-7 using the S"],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells."],"pmcid":["PMC11397358"],"funding_grant_id":["R01 DK122332","Τ2ΕΔΚ 02056"],"pubmed_authors":["Komontachakis G","Liapakis G","Karageorgos V","Vlata Z","Venihaki M","Tselios T","Markatos C","Tsakalakis N","Biniari G","Chepurny OG","Holz GG"],"additional_accession":[]},"is_claimable":false,"name":"Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells.","description":"The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7. The subsequent release of mitoxantrone leads to its intracellular accumulation, thus exerting its cytotoxic effects. To test this hypothesis, we determined the cytotoxic effects of Con-3 and Con-7 using the S","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-07-09T11:10:54.446Z","creation":"2025-04-04T11:35:56.567Z"},"accession":"S-EPMC11397358","cross_references":{"pubmed":["39274973"],"doi":["10.3390/molecules29174127"]}}