Abstract

Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are members of the nuclear receptor superfamily whose effects on cell growth and survival can be modulated therapeutically by small-molecule ligands. Although compounds that target these receptors are powerful anticancer drugs, their use is limited by toxicity. An improved understanding of the structural biology of RXRs and RARs and recent advances in the chemical synthesis of modified retinoid and rexinoid ligands should enable the rational design of more selective agents that might overcome such problems. Here, we review structural data for RXRs and RARs, discuss strategies in the design of selective RXR and RAR modulators, and consider lessons that can be learned for the design of selective nuclear-receptor modulators in general.

Author affiliations

1. Universidade de Vigo, Departamento de Quimica Org´nica, Facultad de Quimica, 36310 Vigo, Spain.
2. INSERM, U554, 34090 Montpellier, France.
3. Université Montpellier 1 et 2, CNRS, UMR5048, Centre de Biochimie Structurale, 34090 Montpellier, France.
4. Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico Luigi de Crecchio 7, 80138, Napoli, Italy.
5. Department of Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 10142, 67404 Illkirch Cedex, France.

Correspondence to: Hinrich Gronemeyer⁵ Email: hg@igbmc.u-strasbg.fr

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