de Lera Angel R, Bourguet William, Altucci Lucia, Gronemeyer Hinrich
Universidade de Vigo, Departamento de Quimica Orgánica, Facultad de Quimica, 36310 Vigo, Spain.
Nat Rev Drug Discov. 2007 Oct;6(10):811-20. doi: 10.1038/nrd2398.
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.
维甲酸受体（RARs）和类视黄醇X受体（RXRs）是核受体超家族的成员，小分子配体可对其对细胞生长和存活的影响进行治疗性调节。尽管靶向这些受体的化合物是强大的抗癌药物，但其使用受到毒性的限制。对RXRs和RARs结构生物学的深入了解以及修饰类视黄醇和类视黄酸X受体配体化学合成的最新进展，应能合理设计出可能克服此类问题的更具选择性的药物。在此，我们综述RXRs和RARs的结构数据，讨论选择性RXR和RAR调节剂的设计策略，并思考从总体上设计选择性核受体调节剂中可吸取的经验教训。
