{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:56:21Z","timestamp":1792018581825,"version":"4.4.0"},"reference-count":97,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie Sklodowska-Curie Actions, of the European Union under Research Executive Agency","award":["101119427"],"award-info":[{"award-number":["101119427"]}]},{"name":"Marie Sklodowska-Curie Actions, of the European Union under Research Executive Agency","award":["EP\/Y030818\/1"],"award-info":[{"award-number":["EP\/Y030818\/1"]}]},{"name":"UK Research and Innovation (UKRI) under the UK government\u2019s Horizon Europe","award":["101119427"],"award-info":[{"award-number":["101119427"]}]},{"name":"UK Research and Innovation (UKRI) under the UK government\u2019s Horizon Europe","award":["EP\/Y030818\/1"],"award-info":[{"award-number":["EP\/Y030818\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>All-trans retinoic acid (ATRA), the major active metabolite of all-trans retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread influence on processes that are crucial to the growth and differentiation of cells and, in turn, the acquisition of mature cell functions. Therefore, there is considerable potential in the use of retinoids to treat diseases. ATRA binds to the retinoic acid receptors (RAR) which, as activated by ATRA, selectively regulate gene expression. There are three main RAR isoforms, RAR\u03b1, RAR\u03b2, and RAR\u03b3. They each have a distinct role, for example, RAR\u03b1 and RAR\u03b3 regulate myeloid progenitor cell differentiation and hematopoietic stem cell maintenance, respectively. Hence, targeting an isoform is crucial to developing retinoid-based therapeutics. In principle, this is exemplified when ATRA is used to treat acute promyelocytic leukemia (PML) and target RAR\u03b1 within PML-RAR\u03b1 oncogenic fusion protein. ATRA with arsenic trioxide has provided a cure for the once highly fatal leukemia. Recent in vitro and in vivo studies of RAR\u03b3 have revealed the potential use of agonists and antagonists to treat diseases as diverse as cancer, heterotopic ossification, psoriasis, and acne. During the final drug development there may be a need to design newer compounds with added modifications to improve solubility, pharmacokinetics, or potency. At the same time, it is important to retain isotype specificity and activity. Examination of the molecular interactions between RAR\u03b3 agonists and the ligand binding domain of RAR\u03b3 has revealed aspects to ligand binding that are crucial to RAR\u03b3 selectivity and compound activity and key to designing newer compounds.<\/jats:p>","DOI":"10.3390\/ijms25126568","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T08:52:10Z","timestamp":1718355130000},"page":"6568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Interactions of Selective Agonists and Antagonists with the Retinoic Acid Receptor \u03b3"],"prefix":"10.3390","volume":"25","author":[{"given":"Katarzyna","family":"Powa\u0142a","sequence":"first","affiliation":[{"name":"Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6781-0329","authenticated-orcid":false,"given":"Teresa","family":"\u017bo\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-0275","authenticated-orcid":false,"given":"Geoffrey","family":"Brown","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-4142","authenticated-orcid":false,"given":"Andrzej","family":"Kutner","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3390\/nu3040385","article-title":"Vitamin A in reproduction and development","volume":"3","author":"Knutson","year":"2011","journal-title":"Nutrients"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mezquita, B., and Mezquita, C. 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