Retinoic acid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [1,6]) are nuclear hormone receptors of the NR1B family activated by the vitamin A-derived agonists tretinoin (ATRA) and alitretinoin, and the RAR-selective synthetic agonists TTNPB and adapalene. BMS493 is a family-selective antagonist [7].

Ro 41-5253 has been suggested to be a PPARγ agonist [14]. LE135 is an antagonist with selectivity for RARα and RARβ compared with RARγ [11].

* Key recommended reading is highlighted with an asterisk

Bour G, Lalevée S, Rochette-Egly C. (2007) Protein kinases and the proteasome join in the combinatorial control of transcription by nuclear retinoic acid receptors. Trends Cell Biol, 17 (6): 302-9. [PMID:17467991]

* Duong V, Rochette-Egly C. (2011) The molecular physiology of nuclear retinoic acid receptors. From health to disease. Biochim Biophys Acta, 1812 (8): 1023-31. [PMID:20970498]

* Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H. (2006) International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev, 58 (4): 712-25. [PMID:17132850]

* Larange A, Cheroutre H. (2016) Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System. Annu Rev Immunol, 34: 369-94. [PMID:27168242]

Maden M. (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci, 8 (10): 755-65. [PMID:17882253]

Mark M, Ghyselinck NB, Chambon P. (2006) Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol, 46: 451-80. [PMID:16402912]

* Saeed A, Hoekstra M, Hoeke MO, Heegsma J, Faber KN. (2017) The interrelationship between bile acid and vitamin A homeostasis. Biochim Biophys Acta, 1862 (5): 496-512. [PMID:28111285]

1. Alexander SPH, Cidlowski JA, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors. Br J Pharmacol, 176 Suppl 1: S229-S246. [PMID:31710718]

2. Apfel C, Bauer F, Crettaz M, Forni L, Kamber M, Kaufmann F, LeMotte P, Pirson W, Klaus M. (1992) A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects. Proc Natl Acad Sci USA, 89 (15): 7129-33. [PMID:1323127]

3. Charpentier B, Bernardon JM, Eustache J, Millois C, Martin B, Michel S, Shroot B. (1995) Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes. J Med Chem, 38 (26): 4993-5006. [PMID:8544175]

4. Charton J, Deprez-Poulain R, Hennuyer N, Tailleux A, Staels B, Deprez B. (2009) Novel non-carboxylic acid retinoids: 1,2,4-oxadiazol-5-one derivatives. Bioorg Med Chem Lett, 19 (2): 489-92. [PMID:19058965]

5. Delescluse C, Cavey MT, Martin B, Bernard BA, Reichert U, Maignan J, Darmon M, Shroot B. (1991) Selective high affinity retinoic acid receptor alpha or beta-gamma ligands. Mol Pharmacol, 40 (4): 556-62. [PMID:1656191]

6. Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H. (2006) International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev, 58 (4): 712-25. [PMID:17132850]

7. Germain P, Gaudon C, Pogenberg V, Sanglier S, Van Dorsselaer A, Royer CA, Lazar MA, Bourguet W, Gronemeyer H. (2009) Differential action on coregulator interaction defines inverse retinoid agonists and neutral antagonists. Chem Biol, 16 (5): 479-89. [PMID:19477412]

8. Géhin M, Vivat V, Wurtz JM, Losson R, Chambon P, Moras D, Gronemeyer H. (1999) Structural basis for engineering of retinoic acid receptor isotype-selective agonists and antagonists. Chem Biol, 6 (8): 519-29. [PMID:10421757]

9. Keidel S, LeMotte P, Apfel C. (1994) Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping. Mol Cell Biol, 14 (1): 287-98. [PMID:8264595]

10. Le Q, Dawson MI, Soprano DR, Soprano KJ. (2000) Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids. Oncogene, 19 (11): 1457-65. [PMID:10723137]

11. Li E. (1999) Structure and function of cytoplasmic retinoid binding proteins. Mol Cell Biochem, 192 (1-2): 105-8. [PMID:10331664]

12. Lund BW, Knapp AE, Piu F, Gauthier NK, Begtrup M, Hacksell U, Olsson R. (2009) Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor beta ligands. J Med Chem, 52 (6): 1540-5. [PMID:19239230]

13. Lund BW, Piu F, Gauthier NK, Eeg A, Currier E, Sherbukhin V, Brann MR, Hacksell U, Olsson R. (2005) Discovery of a potent, orally available, and isoform-selective retinoic acid beta2 receptor agonist. J Med Chem, 48 (24): 7517-9. [PMID:16302793]

14. Schupp M, Curtin JC, Kim RJ, Billin AN, Lazar MA. (2007) A widely used retinoic acid receptor antagonist induces peroxisome proliferator-activated receptor-gamma activity. Mol Pharmacol, 71 (5): 1251-7. [PMID:17290005]

15. Vizirianakis IS, Chatzopoulou M, Bonovolias ID, Nicolaou I, Demopoulos VJ, Tsiftsoglou AS. (2010) Toward the development of innovative bifunctional agents to induce differentiation and to promote apoptosis in leukemia: clinical candidates and perspectives. J Med Chem, 53 (19): 6779-810. [PMID:20925433]