{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:35:14Z","timestamp":1787657714998,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007045","name":"CONAHCyT-SECIHTI","doi-asserted-by":"publisher","award":["CF-2019-171508"],"award-info":[{"award-number":["CF-2019-171508"]}],"id":[{"id":"10.13039\/501100007045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Research into muscle tissue pathologies offers great opportunities for new pharmaceutical agents. Current therapies, including corticosteroids and immunosuppressants, have limited efficacy and significant adverse effects. In this context, steroidal hydrazone compound 4d was investigated for its ability to promote muscle growth and regeneration as a potential anabolic and regenerative modulator. Flow cytometry analysis showed that 4d significantly increases cell populations in S phase, indicating a strong proliferative stimulus in pathways regulated by TNF-\u03b1, AKT, MAFbX, and SMAD2\/3. Molecular docking studies showed that 4d shares strong interactions with the known MasR agonist (EP-2825), exhibiting a higher predicted binding affinity. Furthermore, 4d demonstrated the ability to interact with ACVR1\/2A receptors, mimicking the binding profiles of known antagonists and potentially inhibiting myostatin\/SMAD signaling. Taken together, experimental and computational evidence supports a dual-mechanistic model in which 4d promotes muscle proliferation and regeneration by (1) activating the MasR\u2013PI3K\/AKT\/mTOR axis and (2) inhibiting the ACVR1\/2A\u2013SMAD pathway, counteracting the action of myostatin. These findings position compound 4d as a promising therapeutic candidate against muscle wasting disorders, including cancer-related cachexia, by inducing a robust and multifactorial anabolic response.<\/jats:p>","DOI":"10.3390\/molecules30224486","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:25:27Z","timestamp":1763645127000},"page":"4486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Theoretical-Experimental Analysis to Elucidate the Mechanism of Action of Novel Anabolic Agents"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0545-8232","authenticated-orcid":false,"given":"Israel","family":"Quiroga","sequence":"first","affiliation":[{"name":"Department of Life and Health Sciences, Universidad Popular Aut\u00f3noma del Estado de Puebla, 13 Poniente No. 1927, Barrio de Santiago, Puebla 72410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6114-1670","authenticated-orcid":false,"given":"Maura","family":"Cardenas-Garcia","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Facultad de Medicina, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72420, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-4322","authenticated-orcid":false,"given":"Mar\u00eda Guadalupe","family":"Hern\u00e1ndez-Linares","sequence":"additional","affiliation":[{"name":"Laboratorio de Flujo Continuo y Fotoqu\u00edmica, Centro de Qu\u00edmica, Instituto de Ciencias, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"},{"name":"Laboratorio de Investigaci\u00f3n, Herbario y Jard\u00edn Bot\u00e1nico Universitario, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0332-3785","authenticated-orcid":false,"given":"Gabriel","family":"Guerrero-Luna","sequence":"additional","affiliation":[{"name":"Laboratorio de Flujo Continuo y Fotoqu\u00edmica, Centro de Qu\u00edmica, Instituto de Ciencias, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"},{"name":"Laboratorio de Investigaci\u00f3n, Herbario y Jard\u00edn Bot\u00e1nico Universitario, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-4226","authenticated-orcid":false,"given":"Ferm\u00edn","family":"Flores-Manuel","sequence":"additional","affiliation":[{"name":"Laboratorio de Flujo Continuo y Fotoqu\u00edmica, Centro de Qu\u00edmica, Instituto de Ciencias, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1210\/endrev\/bnaa016","article-title":"Muscle-Organ Crosstalk: The Emerging Roles of Myokines","volume":"41","author":"Severinsen","year":"2020","journal-title":"Endocr. 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