DrugMolDesign, 15 Temple Grove, London NW11 7UA, UK.
Neuroscience Drug Discovery Unit, Wolfson Centre for Age-Related Diseases, Guy's Campus, King's College, London SE1 1UL, UK.
Bioorg Med Chem. 2020 Oct 15;28(20):115664. doi: 10.1016/j.bmc.2020.115664. Epub 2020 Jul 29.
Retinoic acid receptors (RARs) α, β, and γ are members of the nuclear receptor superfamily. Compounds which bind to and activate the RARs are termed retinoids which regulate a wide variety of biological processes such as vertebrate embryonic morphogenesis and organogenesis, cell growth arrest, differentiation, and apoptosis, as well as their disorders. Although many synthetic selective RARα, RARβ, and RARγ agonists have been designed and prepared, these have generally been lipophilic acids without good drug-like properties and with low oral bioavailability. Recently this has been changing and drug design approaches to highly potent and selective RARα and RARβ agonists with low lipophilicity that are orally bioavailable and less toxic have been developed, that have a range of potential therapeutic uses. This review covers these new advances.
视黄酸受体（RARs）α、β 和 γ 是核受体超家族的成员。与 RARs 结合并激活它们的化合物被称为类视黄醇，它们调节广泛的生物学过程，如脊椎动物胚胎形态发生和器官发生、细胞生长停滞、分化和细胞凋亡，以及它们的疾病。尽管已经设计和制备了许多合成的选择性 RARα、RARβ 和 RARγ 激动剂，但这些激动剂通常是亲脂性酸，没有良好的药物样性质和低口服生物利用度。最近这种情况已经发生了变化，人们开发了具有低亲脂性、口服生物利用度高和毒性低的高效选择性 RARα 和 RARβ 激动剂的药物设计方法，这些激动剂具有广泛的潜在治疗用途。这篇综述涵盖了这些新的进展。
