Identification of highly potent retinoic acid receptor α-selective antagonists

Journal of Medicinal Chemistry

Volumn 40, Issue 16, 1997, Pages 2445-2451

  Teng, Min ^a,b   Duong, Tien T ^a   Johnson, Alan T ^a   Klein, Elliott S ^a   Wang, Liming ^a   Khalifa, Berket ^a   Chandraratna, Roshantha A S ^a  

^a ALLERGAN INC   (United States)

^b Alanex Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RETINOIC ACID RECEPTOR; STEROID RECEPTOR;

ALPHA CHAIN; APOPTOSIS; ARTICLE; CELL DIFFERENTIATION; CELL PROLIFERATION; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; MULTIGENE FAMILY; TRANSACTIVATION;

ANIMALS; BENZOATES; CELL LINE; CHROMANS; HAPLORHINI; KINETICS; NAPHTHALENES; RECEPTORS, RETINOIC ACID; RETINOIDS; TRANS-ACTIVATION (GENETICS); TRETINOIN;

EID: 0030875103     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9703911     Document Type: Article

References (32)

1. (a) The Retinoids; Sporn, M. B., Roberts, A. B., Goodman, D. S., Eds.; Academic Press, Inc.: Orlando, FL, 1984.
2. (b) Chemistry and Biology of Synthetic Retinoids; Dawson, M. I., Okamura, W. H., Eds.; CRC Press: Boca Raton, FL, 1990.
3. Evans, R. M. The Steroid and Thyroid Hormone Receptor Superfamily. Science 1988, 240, 889-895.
4. (a) Petkovich, M.; Brand, N. J.; Krust, A.; Chambon, P. A Human Retinoic Acid Receptor Which Belongs to the Family of Nuclear Receptors. Nature 1987, 330, 444-450.
5. (b) Giguere, U.; Ong, E. S.; Segui, P.; Evans, R. M. Identification of a Receptor for the Morphogen Retinoic Acid. Nature 1987, 330, 624-629.
6. (c) Brand, N.; Petkowich, M.; Krust, A.; Chambon, P.; deThe, H.; Marchio, A.; Dejean, A. Identification of a Second Human Retinoic Acid Receptor. Nature 1988, 332, 850-853.
7. γ. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 5310-5314.
8. (a) Mangelsdorf, D. J.; Ong, E. S.; Dyck, J. A.; Evans, R. M. Nuclear Receptor That Identifies A Novel Retinoic Acid Response Pathway. Nature 1990, 345, 224-229.
9. (b) Mangelsdorf, D. J.; Borgmeyer, U.; Heyman, R. A.; Zhou, J. Y.; Ong, E. S.; Oro, A. E.; Kakizuka, A.; Evans, R. M. Characterization of Three RXR Genes That Mediate the Action of 9-cis Retinoic Acid. Genes Dev. 1992, 329-344.
10. β: A Coregulator That Enhances Binding of Retinoic Acid, Thyroid Hormone, and Vitamin D Receptors to Their Cognate Response Elements. Cell 1991, 67, 1251-1266.
11. Boehm, M. F.; Heyman, R. A.; Patel, S.; Stein, R. B.; Nagpal, S. Retinoids: Biological Function and Use in the Treatment of Dermatological Diseases. Exp. Opin. Invest. Drugs 1995, 4, 593-612.
12. Nagpal, S.; Chandraratna, R. A. S. Retinoids as Anti-Cancer Agents. Curr. Pharm. Des. 1996, 2, 295-316.
13. (a) Kamm, J. J. Toxicology, Carcinogenicity, and Teratogenicity of Some Orally Administered Retinoids. J. Am. Acad. Dermatol. 1982, 6, 652-659.
14. (b) Nieman, C.; Klein Obbink, H. J. The Biochemistry and Pathology of Hypervitaminosis A. Vitam. Horm. 1954, 12, 69-99.
15. (a) Fisher, G. J.; Talwar, H. S.; Xiao, J.-H.; Datta, S. C.; Reddy, A. P.; Gaub, M.-P.; Rochette-Egly, C.; Chambon, P.; Voorhees, J. J. Immunological Identification and Functional Quantitation of Retinoic Acid and Retinoid X Receptor Proteins in Human Skin. J. Biol. Chem. 1994, 269, 20629-20635.
16. (b) Dolle, P.; Ruberte, E.; Leroy, P.; Morriss-Kay, G.; Chambon, P. Retinoic Acid Receptors and Cellular Retinoid Binding Proteins 1. A Systematic Study of Their Differential Pattern of Transcription During Mouse Organogenesis. Dev. 1990, 110, 1133-1151.
17. γ-Null F9 Cells Reveals a Partial Functional Redundancy Between the Three RAR Types. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 7854-7858.
18. (a) Johnson, A. T.; Klein, E. S.; Gillett, S. J.; Wang, L.; Song, T. K.; Pino, M. E.; Chandraratna, R. A. S. Synthesis and Characterization of a Highly Potent and Effective Antagonist of Retinoic Acid Receptors. J. Med. Chem. 1995, 38, 4764-4767.
19. (b) Kaneko, S.; Kagechika, H.; Kawachi, E.; Hashimoto, Y.; Shudo, K. Retinoid Antagonists. Med. Chem. Res. 1991, 1, 220-225.
20. (c) Eyrolles, L.; Kagechika, H.; Kawachi, E.; Fukasawa, H.; Iijima, T.; Matsushima, Y.; Hashimoto, Y.; Shudo, K. Retinobenzoic Acids 6. Retinoid Antagonists with a Heterocyclic Ring. J. Med. Chem. 1994, 37, 1508-1517.
21. (d) Yoshimura, H.; Nagai, M.; Hibi, S.; Kikuchi, K.; Abe, S.; Hida, T.; Higashi, S.; Hishinuma, I.; Yamanaka, T. A Novel Type of Retinoic Acid Receptor Antagonist: Synthesis and Structure-Activity Relationships of Heterocyclic Ring-Containing Benzoic Acid Derivatives. J. Med. Chem. 1995, 38, 3163-3173.
22. (e) Fanjul, A.; Dawson, M. I.; Hobbs, P. D.; Jong, L.; Cameron, J. F.; Narlev, E.; Graupner, G.; Lu, X.-P.; Pfahl, M. A New Class of Retinoids with Selective Inhibition of AP-1 Inhibits Proliferation. Nature 1994, 372, 107-111.
23. (f) Chen, J.-Y.; Penco, S.; Ostrowski, J.; Balaguer, P.; Pons, M.; Starrett, J. E., Jr.; Reczek, P.; Chambon, P.; Gronemeyer, H. RAR-Specific Agonist/Antagonists which Dissociate Transactivation and AP-1 Transrepression Inhibit Anchorage-independent Cell Proliferation. EMBO J. 1995, 14, 1187-1197.
24. Apfel, C.; Bauer, F.; Crettaz, M.; Forni, L.; Kamber, M.; Kaufmann, F.; LeMotte, P.; Pirson, W.; Klaus, M. A Retinoic Acid Receptor a Antagonist Selectively Counteracts Retinoic Acid Effects. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7129-7133.
25. (a) Teng, M.; Duong, T. T.; Klein, E. S.; Pino, M. E.; Chandraratna, R. A. S. Identification of a Retinoic Acid Receptor a Subtype Specific Agonist J. Med. Chem. 1996, 39, 3035-3038.
26. (b) The first RARα selective agonists were prepared by Shudo and co-workers: Kagechika, H.; Kawachi, E.; Hashimoto, Y.; Himi, T.; Shudo, K. Retinobenzoic Acids. 1. Structure-Activity Relationships of Aromatic Amides with Retinoidal Activity. J. Med. Chem. 1988, 31, 2182-2192.
27. (a) Heyman, R. A.; Mangelsdorf, D. J.; Dyck, J. A.; Stein, R. B.; Eichele, G.; Evans, R. M.; Thaller, C. 9-Cis Retinoic Acid is a High Affinity Ligand for the Retinoid X Receptor. Cell 1992, 68, 397-406.
28. (b) Christensen, K.; Estes, P. A.; Onate, S. A.; Beck, C. A.; DeMarzo, A. Characterization and Functional Properties of the A and B Forms of Human Progesterone Receptors Synthesized in a Baculovirus System. Mol. Endocrinol. 1991, 5, 1755-1770.
29. 50) of an Enzymatic Reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
30. Klein, E. S.; Pino, M. E.; Johnson, A. T.; Davies, P. J. A.; Nagpal, S.; Thacher, S. M.; Krasinski, G.; Chandraratna, R. A. S. Identification and Functional Separation of Retinoic Acid Receptor Neutral Antagonists and Inverse Agonists. J. Biol. Chem. 1996, 271, 22692-22696.
31. Chen, C.; Okayama, H. High-efficiency Transformation of Mammalian Cells by Plasmid DNA. Mol. Cell Biol. 1987, 7, 2745-2752.
32. De Wet, J. R.; Wood, K. V.; DeLuca, M.; Helinski, D. R.; Subramani, S. Firefly Luciferase Gene: Structure and Expression in Mammalian Cells. Mol. Cell. Biol. 1987, 7, 725-737.