{"id":2307,"date":"2026-05-08T16:38:09","date_gmt":"2026-05-08T14:38:09","guid":{"rendered":"https:\/\/sites.unica.it\/pe2026\/?p=2307"},"modified":"2026-05-08T17:20:45","modified_gmt":"2026-05-08T15:20:45","slug":"ines-lima-carvalho","status":"publish","type":"post","link":"https:\/\/sites.unica.it\/pe2026\/2026\/05\/08\/ines-lima-carvalho\/","title":{"rendered":"In\u00eas Lima Carvalho"},"content":{"rendered":"\n
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PC7 – In\u00eas Lima Carvalho<\/strong><\/p>\n\n\n\n

RISE-Health, Department of Biomedicine, Pharmacology and Therapeutics Unit, Faculty of Medicine, University of Porto, Portugal<\/p>\n\n\n\n

up201904940@fc.up.pt<\/strong><\/p>\n<\/div><\/div>\n\n\n\n

Bioisosteric replacement of the maleimide warhead in a selective covalent NOX4 inhibitor<\/strong><\/strong><\/strong><\/strong><\/td><\/tr>
In\u00eas Lima1<\/sup>, Mariana Castel\u00f4a1<\/sup>, Sofia Benfeito1<\/sup>, Fernanda Borges1,2<\/sup>, Daniel Chavarria1<\/sup><\/em>

1<\/sup><\/em> RISE-Health, Department of Biomedicine, Pharmacology and Therapeutics Unit, Faculty of Medicine, University of Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal
2<\/sup><\/em> RISE-Health, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal<\/td><\/tr>
Abstract<\/strong>
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the seven members of the NOX family and catalyzes the formation of reactive oxygen species. NOX4 has been implicated in neurodegenerative diseases (NDs), being a key player in pathological events such as ferroptosis, neuroinflammation, and protein aggregation [1]. Several small molecules have been identified as NOX inhibitors, but they usually present poor homolog selectivity, assay-interfering effects, unfavourable drug-like properties, and\/or cytotoxicity. Therefore, the development of new selective, non-interfering inhibitors of NOX4 is of upmost importance to clearly understand its biological role and to validate it as a drug target for NDs [2, 3]. Recently, the team developed MAC18, a covalent, selective NOX4 inhibitor with \u00b5M potency, targeting a cysteine residue within the enzyme\u2019s dehydrogenase domain. Structurally, MAC18 is composed of a maleimide warhead and a heterocyclic ring connected through a linker.
As part of our drug discovery program, this work aims at developing MAC18 derivatives bearing maleimide bioisosteres with moderate electrophilicity for NOX inhibition screenings. Following the optimization of the synthetic strategy, a small library of compounds was successfully synthesized. The results obtained so far will be presented in this communication.<\/td><\/tr>
References  <\/strong>
[1] N. Boonpraman, S.S. Yi, NADPH oxidase 4 (NOX4) as a biomarker and therapeutic target in neurodegenerative diseases, Neural. Regen. Res., 19 (2024) 1961\u20131966. https:\/\/doi.org\/10.4103\/1673-5374.390973<\/a>
[2] J. Reis, C. Gorgulla, M. Massari, et al., Targeting ROS production through inhibition of NADPH oxidases, Nat. Chem. Biol., 19 (2023) 1540\u20131550. https:\/\/doi.org\/10.1038\/s41589-023-01457-5<\/a>
[3] J. Reis, M. Massari, S. Marchese, et al., A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action, Redox Biol., 32 (2020)  101466. https:\/\/doi.org\/10.1016\/j.redox.2020.101466<\/a>

Acknowledgments<\/strong>
This work was funded by FEDER funds through the Operational Program Competitiveness Factors COMPETE and national funds by the FCT-Foundation for Science and Technology under research grants for RISE-Health (UID\/06397\/2025, https:\/\/doi.org\/10.54499\/UID\/06397\/2025) and NOXIOUS (EXPL\/BIA-BQM\/0492\/2021 – http:\/\/doi.org\/10.54499\/EXPL\/BIA-BQM\/0492\/2021). This work was also funded by project IMPULSE and services of EU-OPENSCREEN (Horizon Europe: 101132028; DOI: 10.3030\/101132028). M.C. (2022.13356.BD – https:\/\/doi.org\/10.54499\/2022.13356.BD) grant and D.C. (2024.07926.CEECIND) contract were also supported by FCT and FEDER\/COMPETE funds.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n","protected":false},"excerpt":{"rendered":"

PC7 – In\u00eas Lima Carvalho RISE-Health, Department of Biomedicine, Pharmacology and Therapeutics Unit, Faculty of Medicine, University of Porto, Portugal up201904940@fc.up.pt Bioisosteric replacement of the maleimide warhead in a selective covalent NOX4 inhibitor In\u00eas Lima1, Mariana […]<\/p>\n","protected":false},"author":10371,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2307","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2307","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/10371"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=2307"}],"version-history":[{"count":4,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2307\/revisions"}],"predecessor-version":[{"id":2331,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2307\/revisions\/2331"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2307"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2307"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2307"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}