Abstract
Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for biological research, but are also candidate drugs for the treatment of various diseases, including diabetes and allergies, although no RXR antagonist has yet been approved for clinical use. In this review, we present a brief overview of RXR structure, function, and target genes, and describe currently available RXR antagonists, their structural classification, and their evaluation, focusing on the latest research.
Highlights
Among the 48 members of the nuclear receptor superfamily that have identified by sequence aInlti.gJ.nMmoel.nScti.a2n0d18,p1h9,yxl;odgoei:netic tree construction [3,9], 24 are ligand-binding rewcewpwt.omrdsp. iT.cohmes/jeouirnncallu/ijdmes three different subtypes of Retinoid X receptors (RXRs), i.e., RXRα, RXRβ, and RXRγ, which are encoded by distinct genes [3] (Table 1)
In the case of RXR homodimers, the DNA-binding domain (DBD) bind to natural DR1 elements for the calcitonin receptor activity-modifying protein 2 (Ramp2), the NR subfamily 1, group D, member 1 (Nr1d1) and the glycerophospho-diester phosphodiesterase 1 (Gde1) genes, as well as the malic enzyme PPRE gene (MEp) [15,19,20]
Though various RXR antagonists have been reported so far, their antagonistic activity has been evaluated in various ways, i.e., in terms of the dissociation constant (Ki value) using a tritium-labeled ligand such as 9-cis-retinoic acid (1), the binding constant obtained by the SPR method, the Kd value, the IC50 value, and pA2 against an RXR agonist in reporter assays (Tables 3–5)
Summary
Retinoid X receptors (RXRs; NR2B1–3) are nuclear receptors that function either as homodimers or aasshehtetreordoidmimeresrws iwthitohtheorthrecrepretocersptsourcsh sauscpheraosxispoemroexpisroomlifeeraptroorl-iafecrtiavtaotre-dacrteivceaptetdorsre(PcePpAtoRrss; (NPRPA1CR1s–; 3N), Rli1vCer1X–3r)e, cleivpetorrXs (LreXcReps;toNrRs 1(HLX2–R3s);, oNrRfa1rHn2es–o3i)d, oXrrefacrenpetosori(dFXXRr; eNcRep1tHor4)(,FaXnRd;oNthRer1sH[14–), a3n].dRoXtRherhset[e1r–o3d].imReXrsR thheattercoadnimbersactthivatatceadn bbye aRcXtiRvaategdonbiystsRXalRonaegoanreistksnaolwonne asrepkenrmowisnsivaes phertemroisdsimveehrset[e4r]o. d9i-mcise-rRse[t4in].o9i-cciasc-iRdet(i1n,oFiicgaucried 1(1) ,isFiaguproete1n) tisnaatpuortaelnatgnoantuisrtatloawgoarndistRtXoRwsa,rbduRt XalRsso, bwuotrkaslsoaswaonrakcstiavsataonr aocftrivetaitnooricofacriedtinreociecpatcoirds r(RecAeRptso)r[s5](.RTAhResR) X[5R]. syTnhteheRtiXcRagsoynnitshtebtiecxargootneniset b(LeGxaDro1t0e6n9e, (TLaGrgDr1e0ti6n9®,,T2a,rFgirgeutirne®1, )2,isFiugsuerde 1fo)risthuesetdrefaotrmthenettroefactmuteannteofucsuTtacneelol ulysmTpchelolmlyam(pChToCmLa) ([C6]T, CbuLt), [o6n],tbhueto, tohnertheanodth, nero hRaXnRd,antoagRoXnRistanhtaasgyoentisetnhtearsedyectliennictaelreudsec,lienviecnalthuoseu,gehvaenntit-htyopuegh adniatbi-etytepse [27]diaanbdeteasn[t7i-]aallnedrgayntaic-atilvleitrigeys a[8ct]ivhiativees [b8e]ehnavfoeubnedeninfouandiminalamniomdaellsm. oAdtelpsr.eAsetnptr,eRseXnRt, RanXtRagaonntiasgtsonarisetsmaarienmlyaeimnlpyleomyepdloayseadnaaslyatnicaallytiocoallstoinolsstuindisetsudoifeRs XoRf RfXunRcftuionnc.tiIonnt.hIins trheivsierewv,iewwe, weillwfilrlsfit rpsrtepsreensteantbariberfioefvoervveirevwiewofothf tehReXRRXRstsrutrcutcutruer,ef,ufuncntcitoinon, a, annddtatarrggeettggeenneess,,aannddtthheenn describe currently available RXR antagonists, their structural classiffiication, and their evaluation, focusing on the latest research. CChheemmiiccaall ssttrruuccttuurreess ooff 99--cciiss--rreettiinnooiicc aacciidd ((11)) aanndd bbeexxaarrootteennee ((22))
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
