{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T07:43:59Z","timestamp":1768722239446,"version":"3.49.0"},"reference-count":337,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"PT national funds","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The inadequate vascularization seen in fast-growing solid tumors gives rise to hypoxic areas, fostering specific changes in gene expression that bolster tumor cell survival and metastasis, ultimately leading to unfavorable clinical prognoses across different cancer types. Hypoxia-inducible factors (HIF-1 and HIF-2) emerge as druggable pivotal players orchestrating tumor metastasis and angiogenesis, thus positioning them as prime targets for cancer treatment. A range of HIF inhibitors, notably natural compounds originating from marine organisms, exhibit encouraging anticancer properties, underscoring their significance as promising therapeutic options. Bioprospection of the marine environment is now a well-settled approach to the discovery and development of anticancer agents that might have their medicinal chemistry developed into clinical candidates. However, despite the massive increase in the number of marine natural products classified as \u2018anticancer leads,\u2019 most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.<\/jats:p>","DOI":"10.3390\/md22040143","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:28:06Z","timestamp":1711369686000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0914-1734","authenticated-orcid":false,"given":"Maria Rita","family":"Garcia","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"1H-TOXRUN-Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\/REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Florence","family":"Lefranc","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, H\u00f4pital Universitaire de Bruxelles (H.U.B), CUB H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-9678","authenticated-orcid":false,"given":"Nelson G. M.","family":"Gomes","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106391","DOI":"10.1016\/j.phrs.2022.106391","article-title":"Marine Pharmacology in 2018: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action","volume":"183","author":"Mayer","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1039\/D2NP00083K","article-title":"Marine Natural Products","volume":"40","author":"Carroll","year":"2023","journal-title":"Nat. Prod. 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