{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:14:16Z","timestamp":1776773656267,"version":"3.51.2"},"reference-count":124,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007045","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI) M\u00e9xico","doi-asserted-by":"publisher","award":["CBF-2025-I-3360"],"award-info":[{"award-number":["CBF-2025-I-3360"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto Polit\u00e9cnico","award":["SIP-20251062"],"award-info":[{"award-number":["SIP-20251062"]}]},{"name":"SECIHTI","award":["958659"],"award-info":[{"award-number":["958659"]}]},{"name":"Bordeaux, France","award":["ECOS-NORD M18S01"],"award-info":[{"award-number":["ECOS-NORD M18S01"]}]},{"name":"Instituto Polit\u00e9cnico Nacional (SIP-IPN), M\u00e9xico","award":["Pro25DTIA-2025-A293"],"award-info":[{"award-number":["Pro25DTIA-2025-A293"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer (BC) is a malignant tumor that develops in the mammary gland due to uncontrolled cell proliferation. Estrogen receptor (ER) signaling, mediated by 17\u03b2-estradiol (E2), plays a crucial role in regulating cell proliferation, differentiation, and survival. Specifically, the binding of E2 to the estrogen receptor alpha (ER\u03b1) increases cell proliferation. Conversely, selective estrogen receptor beta (ER\u03b2) agonists inhibit cancer cell proliferation by suppressing the expression of oncogenes, making ER\u03b2 an important therapeutic target. Given the urgent need for targeted and effective therapies for BC, we implemented a strategy based on multicomplex pharmacophores modeling of ER\u03b2 (MPMER\u03b2) and ER\u03b1 (MPMER\u03b1), performing a virtual cross-screening of databases of clinically approved and experimental drugs to identify those with high affinity and stereoelectronic complementarity with the ER\u03b2 agonist pharmacophore hypothesis. The implementation of a chemoinformatic strategy enabled the identification of Sobetirome, Labetalol, and Procaterol as molecular hits on the ER\u03b2 pharmacophore map. Procaterol showed the most significant antiproliferative activity in vitro assays, with IC50 values of 21.26 and 36.10 \u00b5M in MCF-7 and MDA-MB-231, respectively. It is imperative to note that these findings require experimental validation of the ER\u03b2 activation pathways to strengthen the possible therapeutic repurposing of the drugs selected through our in silico approach. Finally, this strategy not only facilitates drug repurposing under in silico simulation but also provides valuable information for the rational design of new drugs against BC.<\/jats:p>","DOI":"10.3390\/ijms27010463","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T11:11:46Z","timestamp":1767352306000},"page":"463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multicomplex Pharmacophore Modeling of Estrogen Receptors Suggests the Probable Repurposing of Procaterol as an Antiproliferative Agent Against Breast Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0219-3139","authenticated-orcid":false,"given":"Luis Heriberto","family":"Vazquez-Mendoza","sequence":"first","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), Escuela Superior de Medicina del Instituto Polit\u00e9cnico Nacional (ESM-IPN), Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-4281","authenticated-orcid":false,"given":"Humberto L.","family":"Mendoza-Figueroa","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), Escuela Superior de Medicina del Instituto Polit\u00e9cnico Nacional (ESM-IPN), Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-3774","authenticated-orcid":false,"given":"Nadia Judith","family":"Jacobo-Herrera","sequence":"additional","affiliation":[{"name":"Unidad de Bioqu\u00edmica, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-5891","authenticated-orcid":false,"given":"Norbert","family":"Bakalara","sequence":"additional","affiliation":[{"name":"Ecole Nationale Sup\u00e9rieure de Technologie des Biomol\u00e9cules de Bordeaux (ENSTBB), Universit\u00e9 de Bordeaux, CNRS, Bordeaux INP, CBMN, UMR 5248, F-33600 Pessac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-2726","authenticated-orcid":false,"given":"Daphne Edith","family":"Gonz\u00e1lez-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Biolog\u00eda Molecular, Instituto Potosino de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (DBM-IPICYT), y Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI), San Luis Potos\u00ed 78216, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-5265","authenticated-orcid":false,"given":"Jos\u00e9","family":"Correa-Basurto","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), Escuela Superior de Medicina del Instituto Polit\u00e9cnico Nacional (ESM-IPN), Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1930-5288","authenticated-orcid":false,"given":"Juan Benjam\u00edn","family":"Garc\u00eda-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), Escuela Superior de Medicina del Instituto Polit\u00e9cnico Nacional (ESM-IPN), Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"},{"name":"Investigadoras e Investigadores por M\u00e9xico SECIHTI -Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n de la Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","unstructured":"CDC (2025, July 01). 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