Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review

TY - JOUR

T1 - Recent advances in the design of RAR α and RAR β agonists as orally bioavailable drugs. A review

AU - Borthwick, Alan D.

AU - Goncalves, Maria B.

AU - Corcoran, Jonathan P.T.

PY - 2020/10/15

Y1 - 2020/10/15

N2 - 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.

AB - 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.

KW - AC-261066

KW - Alpha agonist

KW - Beta agonist

KW - C286

KW - Nerve injury

KW - RAR586

KW - Retinoic acid receptor

KW - SAR

UR - http://www.scopus.com/inward/record.url?scp=85089225224&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2020.115664

DO - 10.1016/j.bmc.2020.115664

M3 - Review article

AN - SCOPUS:85089225224

SN - 0968-0896

VL - 28

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 20

M1 - 115664

ER -