Current and future development of estrogen receptor ligands: Applications in estrogen-related cancers

Recent Patents on Endocrine, Metabolic and Immune Drug Discovery

Volumn 5, Issue 3, 2011, Pages 210-229

  Bolli, Alessandro ^a   Marino, Maria ^a  

^a ROMA TRE UNIVERSITY   (Italy)

Author keywords

Agonists; Antagonists; Cancer; Estrogen receptor alpha; Estrogen receptor beta; SERMs

Indexed keywords

21 (4 DIETHYLAMINOMETHYL 2 METHOXYPHENOXY) 7ALPHA METHYL 19 NORPREGNA 1,3,5(10) TRIEN 3 OL; 4 (1,2 DIPHENYL 1 BUTENYL)CINNAMIC ACID; 4 [4 METHYL 2 [4 [2 (1 PIPERIDINYL)ETHOXY]PHENYL] 7 PIVALOYLOXY 2H 1 BENZOPYRAN 3 YLPHENYL] PIVALATE; 4 HYDROXY N DESMETHYL TAMOXIFEN; 4 HYDROXY TAMOXIFEN; ACOLBIFENE; ACTINO POLYMORPHOL A; ANTINEOPLASTIC AGENT; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR LIGAND; FULVESTRANT; GW 7604; NARINGENIN; PYRIMIDINE; RALOXIFENE; SR 16388; TAMOXIFEN CITRATE; TAMOXIFEN DERIVATIVE; TOREMIFENE; TRIPHENYL ALKENE DERIVATIVE; UNCLASSIFIED DRUG; ZK 253; ZK 703;

AMINO ACID SEQUENCE; BREAST CANCER; CELL PROLIFERATION; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; DRUG TARGETING; ESTROGEN RELATED CANCER; GENE LOCUS; GENOME; HORMONE STRUCTURE; HUMAN; MEDICAL LITERATURE; MOLECULAR MECHANICS; NEOPLASM; NONHUMAN; PATENT; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; STRUCTURE ACTIVITY RELATION; TRANSACTIVATION;

ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; HUMANS; LIGANDS; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; NEOPLASMS, HORMONE-DEPENDENT; PATENTS AS TOPIC;

EID: 80052835714     PISSN: 18722148     EISSN: None     Source Type: Journal    
DOI: 10.2174/187221411797265881     Document Type: Review

References (168)

1. Ascenzi P, Bocedi A, Marino M. Structure-function relationship of estrogen receptor α and β: Impact on human health. Mol Aspects Med 2006; 4: 299-402.
2. Nilsson S, Gustafsson JÅ. Estrogen receptors: Therapies targeted to receptor subtypes. Clin Pharmacol Ther 2011; 89: 44-55.
3. Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics 2006; 7: 497-508.
4. Henderson BE, Feigelson HS. Hormonal carcinogenesis. Carcinogenesis 2000; 21: 427-33.
5. McEwan IJ. In: McEwan IJ Eds. Essay in Biochemistry: The Nuclear Receptor Superfamily. London: Portland Press 2004: 1-10.
6. Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest 2006; 116: 561-70.
7. Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: From a phenotypical to a molecular-based classification. Virchows Arch 2004; 444: 213-23.
8. Steiner MS, Raghow S. Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk. World J Urol 2003; 21: 31-6.
9. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. American Cancer Society. Cancer statistics 2004. CA Cancer J Clin 2004; 54: 8-29.
10. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33.
11. Konstantinopoulos PA, Kominea A, Vandoros G, Sykiotis GP, Andricopoulos P, Varakis I, et al. Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer 2003; 39: 1251-8.
12. Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P. Loss of ERβ expression as a common step in estrogen -dependent tumor progression. Endocr Relat Cancer 2004; 11: 537-51.
13. Jassam N, Bell SM, Speirs V, Quirke P. Loss of expression of oestrogen receptor β in colon cancer and its association with Dukes' staging. Oncol Rep 2005; 14: 17-21.
14. Galluzzo P, Caiazza F, Moreno S, Marino M. Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation. Endocr Relat Cancer 2007; 14: 153-67.
15. Barone M, Scavo MP, Papagni S, Piscitelli D, Guido R, Di Lena M, et al. ERβ expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis. Scand J Gastroenterol 2010; 45: 1320-8.
16. Warner M, Gustafsson J-Å. The role of estrogen receptor β (ERβ) in malignant diseases--a new potential target for antiproliferative drugs in prevention and treatment of cancer. Biochem Biophys Res Commun 2010; 396:63-6.
17. Pettersson K, Delaunay F, Gustafsson J-Å. Estrogen receptor β acts as a dominant regulator of estrogen signaling. Oncogene 2000; 19: 4970-8.
18. Koehler KF, Helguero LA, Haldosen LA, Warner M, Gustafsson J-Å. Reflections on the discovery and significance of estrogen receptor β. Endocr Rev 2005; 26: 465-78.
19. Gosden JR, Middleton PG, Rout D. Localization of the human oestrogen receptor gene to chromosome 6q24-q27 by in situ hybridization. Cytogenet Cell Genet 1986; 43: 218-20.
20. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson, J.-A. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Nat Acad Sci USA 1996; 93: 5925-30.
21. Mosselman S, Polman J, Dijkema R. ERβ: Identification and characterization of a novel human estrogen receptor. FEBS Lett 1996; 392: 49-53.
22. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, et al. Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 1997; 82: 4258-65.
23. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 1997; 138: 863-70.
24. Claessens F, Gewirth DT. In: McEwan IJ. Ed. Essay in Biochemistry: The Nuclear Receptor Superfamily. London: Portland Press 2004: 59-72.
25. Kumar R, Johnson BH, Thompson EB. In: McEwan IJ. Ed. Essay in Biochemistry: The Nuclear Receptor Superfamily. London: Portland Press 2004: 27-39.
26. Gruber CJ, Gruber DM, Gruber IM, Wieser F, Huber JC. Anatomy of the estrogen response element. Trends Endocrinol Metab 2004; 15: 73-8.
27. Beato M. Gene regulation by steroid hormones. Cell 1989; 56: 335-44
28. Auboeuf D, Hönig A, Berget SM, O'Malley BW. Coordinate regulation of transcription and splicing by steroid receptor coregulators. Science 1999; 298: 416-9.
29. Lonard DM, Nawaz Z, Smith CL, O'Malley BW. The 26S proteasome is required for estrogen receptor-α and coactivator turnover and for efficient estrogen receptor α transactivation. Mol Cell 2000; 5: 939-48.
30. Göttlicher M, Heck S, Herrlich P. Transcriptional cross-talk, the second mode of steroid hormone receptor action. J Mol Med 1998; 76: 480-9.
31. O'Lone R, Frith MC, Karlsson EK, Hansen U. Genomic targets of nuclear estrogen receptors. Mol Endocrinol 2004; 18: 1859-75.
32. Gaub MP, Bellard M, Scheuer I, Chambon P, Sassone-Corsi P. Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. Cell 1990; 3: 1267-76.
33. Galien R, Garcia T. Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-κB site. Nucleic Acids Res 1997; 25: 2424-9.
34. Jacob J, Sebastian KS, Devassy S, Priyadarsini L, Farook MF, Shameem A, et al. Membrane estrogen receptors: Genomic actions and post transcriptional regulation. Mol Cell Endocrinol 2006; 246: 34-41.
35. Song RX, Barnes CJ, Zhang Z, Bao Y, Kumar R, Santen RJ. The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor α to the plasma membrane. Proc Natl Acad Sci USA 2004; 101: 2076-81.
36. Marino M, Ascenzi P. Membrane association of estrogen receptor α and β influences 17β-estradiol-mediated cancer cell proliferation. Steroids 2008; 73: 853-8.
37. Pike ACW, Brzozowski AM, Hubbard RE. A structural biologist's view of the oestrogen receptor. J Steroid Biochem Mol Biol 2000; 7: 261-8.
38. Ariazi EA, Ariani JL, Cordera F, Jordan VC. Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem 2006; 6: 195-216.
39. Smith CL, O'Malley BW. Coregulator function: A key to understanding tissue specificity of selective receptor modulators. Endocr Rev 2004; 25: 45-71.
40. Pike ACW, Brzozowski AM, Walton J, Hubbard RE, Thorsell AG, Li YL, et al. Structural insights into the mode of action of a pure antiestrogen. Structure 2001; 9: 145-53.
41. McDonnell DP. The molecular pharmacology of SERMs. Trends Endocrinol Metab 1999; 10: 301-11.
42. Jordan, V.C. Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 1. Receptor interactions. J Med Chem 2003a; 46: 883-908.
43. Jordan, V.C. Antiestrogens and selective estrogen receptor modulators as multifunctional medicines. 2. Clinical considerations and new agents. J Med Chem 2003b; 46: 1081-1111
44. Jordan VC, O'Malley BW. Selective estrogen-receptor modulators and anti hormonal resistance in breast cancer. J Clin Oncol 2007; 25: 5815-24.
45. Song RX, Fan P, Yue W, Chen Y, Santen RJ. Role of receptor complexes in the extranuclear actions of estrogen receptor α in breast cancer. Endocr Relat Cancer 2006; 13: 3-13.
46. Acconcia F, Totta P, Ogawa S, Cardillo I, Inoue S, Leone S, et al. Survival versus apoptotic 17β-estradiol effect: Role of ERα and ERβ activated non-genomic signalling. J Cell Physiol 2005; 203: 193-201.
47. Galluzzo P, Ascenzi P, Bulzomi P, Marino M. The nutritional flavanone naringenin triggers antiestrogenic effects by regulating estrogen receptor α-palmitoylation. Endocrinology 2008; 149: 2567-75.
48. Bolli A, Galluzzo P, Ascenzi P, Del Pozzo G, Manco I, Vietri MT, et al. Laccase treatment impairs bisphenol A-induced cancer cell proliferation affecting estrogen receptor α-dependent rapid signals. IUBMB Life 2008; 60: 843-52.
49. Bolli A, Bulzomi P, Galluzzo P, Acconcia F, Marino M. Bisphenol A impairs estradiol-induced protective effects against DLD-1 colon cancer cell growth. IUBMB Life 2010; 62: 684-7.
50. Métivier R, Stark A, Flouriot G, Hübner MR, Brand H, Penot G, et al. A dynamic structural model for estrogen receptor α activation by ligands, emphasizing the role of interactions between distant A and E domains. Mol Cell 2002; 10: 1019-32.
51. Terasaka S, Aita Y, Inoue A, Hayashi S, Nishigaki M, Aoyagi K, et al. Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals. Environ Health Perspect 2004; 112: 773-81.
52. Castoria G, Migliaccio A, Bilancio A, Di Domenico M, de Falco A, Lombardi M, et al. PI3-kinase in concert with Src promotes the Sphase entry of oestradiol-stimulated MCF-7 cells. EMBO J 2001; 20: 6050-9.
53. Wu H, Chen Y, Liang J, Shi B, Wu G, Zhang Y, et al. Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 2005; 438: 981-7.
54. Maulbecker CC, Gruss P. The oncogenic potential of Pax genes. EMBO J 1993; 12: 2361-7.
55. Razandi M, Pedram A, Levin ER. Estrogen signals to preservation of endothelial cell form and function. J Biol Chem 2000; 275: 38540-6.
56. Marino M, Acconcia F, Bresciani F, Weisz A, Trentalance A. Distinct nongenomic signal transduction pathways controlled by 17β- estradiol regulate DNA synthesis and cyclin D1 gene transcription in HepG2 cells. Mol Biol Cell 2002; 13: 3720-9.
57. Marino, M, Acconcia F, Trentalance A. Biphasic estradiol induced AKT-phosphorylation is modulated by PTEN via MAP kinase in HepG2 cells. Mol Biol Cell 2003; 14: 2583-91.
58. Clarke R, Liu MC, Bouker KB, Gu Z, Lee RY, Zhu Y, et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 2003; 22: 7316-39.
59. Normanno N, Di Maio M, De Maio E, De Luca A, de Matteis A, Giordano A, et al. Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr Relat Cancer 2005; 12: 721-47.
60. Fan P, Wang J, Santen RJ, Yue W. Long-term treatment with tamoxifen facilitates translocation of estrogen receptor α out of the nucleus and enhances its interaction with EGFR in MCF-7 breast cancer cells. Cancer Res 2007; 67: 1352-60.
61. Korach KS, Emmen JM, Walker VR, Hewitt SC, Yates M, Hall JM, et al. Update on animal models developed for analyses of estrogen receptor biological activity. J Steroid Biochem Mol Biol 2003; 86: 387-91.
62. Matthews J, Gustafsson J-Å. Estrogen signalling: A subtle balance between ERα and ERβ. Mol Interventions 2003; 3: 281-92.
63. Saville B, Wormke M, Wang F, Nguyen T, Enmark E, Kuiper G, et al. 2000. Ligand-, cell-, and estrogen receptor subtype (α/β)-dependent activation at GC-rich (Sp1) promoter elements. J Biol Chem 2000; 275: 5379-87.
64. Caiazza F, Galluzzo P, Lorenzetti S, Marino M. 17β-Estradiol induces ERβ up-regulation via p38/MAPK activation in colon cancer cells. Biochem Biophys Res Commun 2007; 359: 102-7.
65. Fixemer T, Remberger K, Bonkhoff H. Differential expression of the estrogen receptor β (ERβ) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma. Prostate 2003; 54: 79-87.
66. Signoretti S, Loda M. Estrogen receptor β in prostate cancer: brake pedal or accelerator? Am J Pathol 2001; 159: 13-6.
67. Cheng J, Lee EJ, Madison LD, Lazennec G. Expression of estrogen receptor β in prostate carcinoma cells inhibits invasion and proliferation and triggers apoptosis. FEBS Lett 2004; 566: 169-72.
68. Couse JF, Korach KS. Estrogen receptor α mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the murine reproductive tract. Toxicology 2004; 205: 55-63.
69. Pravettoni A, Mornati O, Martini PG, Marino M, Colciago A, Celotti F, et al. Estrogen receptor β (ERβ) and inhibition of prostate cancer cell proliferation: studies on the possible mechanism of action in DU145 cells. Mol Cell Endocrinol 2007; 263: 46-54.
70. Zhang G, Liu X, Farkas AM, Parwani AV, Lathrop KL, Lenzner D, et al. Estrogen receptor β functions through nongenomic mechanisms in lung cancer cells. Mol Endocrinol 2009; 23: 146-56.
71. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371-1388.
72. Fisher B, Dignam J, Wolmark N, Wickerham DL, Fisher ER, Mamounas E, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 1999 353: 1993-2000.
73. Kristensen B, Ejlertsen B, Dalgaard P, Larsen L, Holmegaard SN, Transbøl I, et al. Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: A randomized study. J Clin Oncol 1994; 12: 992-7.
74. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Tamoxifen for early breast cancer: An overview of the randomised trials, Lancet 1998; 351: 1451-67.
75. Hellmann-Blumberg U, Taras TL, Wurz GT, DeGregorio MW. Genotoxic effects of the novel mixed antiestrogen FC-1271a in comparison to tamoxifen and toremifene. Breast Cancer Res Treat 2000; 60: 63-70.
76. Phillips DH. Understanding the genotoxicity of tamoxifen? Carcinogenesis 2001; 22: 839-49.
77. Shang Y, Brown M. Molecular determinants for the tissue specificity of SERMs. Science 2002; 295: 2465-8.
78. Brauch H, Mürdter TE, Eichelbaum M, Schwab M. Pharmacogenomics of tamoxifen therapy. Clin Chem 2009; 55: 1770-82.
79. Raghow S, Hooshdaran MZ, Katiyar S, Steiner MS. Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model. Cancer Res 2002; 62: 1370-6.
80. Nicholson RI, Gee JM, Manning DL, Wakeling AE, Montano MM, Katzenellenbogen BS. Responses to pure antiestrogens (ICI 164384, ICI 182780) in estrogen-sensitive and -resistant experimental and clinical breast cancer. Ann NY Acad Sci 2005; 761: 148-63.
81. McInerney EM, Weis KE, Sun J, Mosselman S, Katzenellenbogen BS. Transcription activation by the human estrogen receptor subtype β (ERβ) studied with ERβ and ERα receptor chimeras. Endocrinology 1998; 139: 4513-22.
82. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S. Differential response of estrogen receptor α and estrogen receptor β to partial estrogen agonists/antagonists. Mol Pharmacol 1998; 54:105-12.
83. Zhou JH, Yu DV, Cheng J, Shapiro DJ. Delayed and persistent ERK1/2 activation is required for 4-hydroxytamoxifen-induced cell death. Steroids 2007; 11-12: 765-77.
84. Flamini MI, Sanchez AM, Goglia L, Tosi V, Genazzani AR, Simoncini T. Differential actions of estrogen and SERMs in regulation of the actin cytoskeleton of endometrial cells. Mol Hum Reprod 2009; 15: 675-85.
85. Gielen SC, Santegoets LA, Kühne LC, Van Ijcken WF, Boers-Sijmons B,Hanifi-Moghaddam P, et al. Genomic and nongenomic effects of estrogen signaling in human endometrial cells: Involvement of the growth factor receptor signaling downstream AKT pathway. Reprod Sci 2007; 14: 646-54.
86. Johnson MD, Westley BR, May FE. Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells. Br J Cancer 1989; 59: 727-38.
87. Johnson MD, Zuo H, Lee KH, Trebley JP, Rae JM, Weatherman RV, et al. Pharmacological characterization of 4-hydroxy-Ndesmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004; 85: 151-9.
88. Lim YC, Li L, Desta Z, Zhao Q, Rae JM, Flockhart DA, et al. Endoxifen, a secondary metabolite of tamoxifen, and 4-OH-tamoxifen induce similar changes in global gene expression patterns in MCF-7 breast cancer cells. J Pharmacol Exp Ther 2006; 318: 503-12.
89. Dodge JA, Lugar CW, Cho S, Short LL, Sato M, Yang NN, et al. Evaluation of the major metabolites of raloxifene as modulators of tissue selectivity. J Steroid Biochem Mol Biol 1997; 61: 97-106.
90. Escande A, Pillon A, Servant N, Cravedi JP, Larrea F, Muhn P, et al. Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta. Biochem Pharmacol 2006; 71: 1459-69.
91. Rossi V, Bellastella G, De Rosa C, Abbondanza C, Visconti D, Maione L, et al. Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptor α and β. J Cell Physiol 2011; 226: 1334-9.
92. Zhang YX, Kong CZ. The role of mitogen-activated protein kinase cascades in inhibition of proliferation in human prostate carcinoma cells by raloxifene: An in vitro experiment. Zhonghua Yi Xue Za Zhi 2008; 88: 271-5.
93. Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-Year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 2001; 65: 125-34.
94. Grady D, Cauley JA, Stock JL, Cox DA, Mitlak BH, Song J, et al. Effect of Raloxifene on all-causemortality. Am J Med 2010; 123: 469.e1-7.
95. Howell SJ, Johnston SR, Howell A. The use of selective estrogen receptor modulators and selective estrogen receptor downregulators in breast cancer, Best Pract Res Clin Endocrinol Metab 2004; 18: 47-66.
96. Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, et al. Toremifene-a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs 2006; 15: 293-305.
97. Price D, Stein B, Sieber P, Tutrone R, Bailen J, Goluboff E, et al. Toremifene for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: Results of a double-blind, placebo controlled, phase IIB clinical trial. J Urol 2006; 176: 965-71.
98. Wakeling AE, Dukes M, Bowler J. A potent specific pure antiestrogen with clinical potential. Cancer Res 1991; 51: 3867-73.
99. Johnston SJ, Cheung KL. Fulvestrant - a novel endocrine therapy for breast cancer. Curr Med Chem 2010; 17: 902-14.
100. Dauvois S, White R, Parker MG. The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci 1993; 106: 1377-88.
101. Hu XF, Veroni M, De Luise M, Wakeling A, Sutherland R, Watts CK, et al. Circumvention of tamoxifen resistance by the pure antiestrogen ICI 182,780. Int J Cancer 1993; 55: 873-6.
102. Bundred NJ, Anderson E, Nicholson RI, Dowsett M, Dixon M, Robertson JF. Fulvestrant, an estrogen receptor downregulator, reduces cell turnover index more effectively than tamoxifen. Anticancer Res 2002; 22: 2317-9.
103. Bross PF, Cohen MH, Williams GA, Pazdur R. FDA drug approval summaries: Fulvestrant. Oncologist 2002; 7: 477-80.
104. Croxtall JD, McKeage K. Fulvestrant: A review of its use in the management of hormone receptor-positive metastatic breast cancer in postmenopausal women. Drugs 2011; 71: 363-80.
105. Kaltenbach, R. F., Robinson, S. P., Trainor, G. L. Selective estrogen receptor modulators. US7045540 (2005).
106. Loozen, H. J. J. 16,17-carbocyclic condensed steroid compounds having selective estrogenic activity. US7868193 (2011).
107. Welsh, W. J., Wang, N. C. Y., Ai, N. Estrogen receptor modulators and uses thereof. US20100152271 (2010).
108. Danso-danquah, R., Abraham, D. J., Lin, H.-R., Burnett, J. C. Compounds having antiestrogenic and tissue selective estrogenic properties, and compounds with anti-androgenic properties for treatment of prostate cancer and androgen receptor dependent diseases. US7601739 (2009).
109. Jain, N. F., Macielag, M. J., Murray, W. V., Ng, R. A., Sui, Z. Cyclohexyl derivatives as selective estrogen receptor modulators. US7183445 (2007).
110. Zhang, X., Sui, Z. Novel Spiro-benzo[c]chromene derivatives useful as modulators of the estrogen receptors. US20090069362 (2009).
111. Gayo-fung, L. M., Stein, B. M. Compounds and methods for modulation of estrogen receptors. US7435729 (2008).
112. Cooperwood, J. S. Selective estrogen receptor modulators. US7687486 (2010).
113. Schmidt, J. M., Mercure, J., Lowell, J. L., Kwiatkowski, S., Pupek, K., Zhu, S., Whelan, J., Lazarowych, N. Non-steroidal estrogen receptor ligands. US6599921 (2003).
114. Hajela, K., Jha, A. K., Singh, M. M., Jain, G. K., Balapure, A. K., Dwivedy, A., Agarwal, B., Murthy, P. S. R. Novel-N substituted dihydrobenzothiepino, dihydrobenzoxepino and tetrahydro benzocyclohepta indoles as selective estrogen receptor modulators. US20050282863 (2005).
115. Södervall, M.-l., Kalapudas, A., Kangas, L., Lammintausta, R., Härkönen, P., Väänänen, K., Karjalainen, A. Triphenylalkene derivatives and their use as selective estrogen receptor modulators. US6875775 (2005).
116. McDonnell, D. P. Norris, J., Connor, C., Wijayaratne, A. A method of preventing or treating estrogen-dependent diseases and disorders. WO9908682 (1999).
117. Weatherman RV, Clegg NJ, Scanlan TS. Differential SERM activation of the estrogen receptors (ERα and ERβ) at AP-1 sites. Chem Biol 2001 May;8(5):427-36.
118. Bentrem D, Dardes R, Liu H, MacGregor-Schafer J, Zapf J, Jordan V. Molecular mechanism of action at estrogen receptor α of a new clinically relevant antiestrogen (GW7604) related to tamoxifen. Endocrinology 2001; 142: 838-46.
119. Labrie, F., Merand, Y., Gauthier, S. Benzopyran-containing compounds and method for their use. US6060503 (2000).
120. Gauthier S, Caron B, Cloutier J, Dory YL, Favre A, Larouche D, et al. (S)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2(1-piperidinyl)-ethoxy] phenyl]-2H-1-benzopyran-3-yl]-phenyl 2, 2 - Dimethylpropanoate (EM-800): A highly potent, specific, and orally active nonsteroidal antiestrogen. J Med Chem 1997; 40: 2117-22.
121. Tremblay A, Tremblay GB, Labrie C, Labrie F, Giguère V. EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors α and β. Endocrinology 1998; 139: 111-8.
122. Labrie F, Labrie C, Bélanger A, Simard J, Gauthier S, Luu-The V, et al. EM-652 (SCH57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium. J Steroid Biochem Mol Biol 1999; 69: 51-84.
123. Simoncini T, Varone G, Fornari L, Mannella P, Luisi M, Labrie F, et al. Genomic and nongenomic mechanisms of nitric oxide synthesis induction in human endothelial cells by a fourth-generation selective estrogen receptor modulator. Endocrinology 2002; 143: 2052-61.
124. Couillard S, Labrie C, Gauthier S, Merand Y, Singh SM, Candas B, et al. Long-term inhibitory effect of the orally active and pure antiestrogen EM-800 on the growth of human breast cancer xenografts in nude mice. Int J Cancer. 2000; 85: 424-9.
125. Bohlmann R, Bittler D, Fritzemeier KH, Heinrich N, Hoffmann J, Hofmeister H, et al. Novel 7 alkylamino substituted estradiol derivatives with pure antiestrogenic activity following oral administration. J Cancer Res Clin Oncol 2001; 127: S42.
126. Hoffmann J, Bohlmann R, Heinrich N, Hofmeister H, Kroll J, Künzer H, et al. Characterization of new estrogen receptor destabilizing compounds: Effects on estrogensensitive and tamoxifenresistant breast cancer. J Natl Cancer Inst 2004; 96: 210-8.
127. Yamamoto Y, Wada O, Takada I, Yogiashi Y, Shibata J, Yanagisawa J, et al. Both Nand C-terminal transactivation functions of DNA-bound ERα are blocked by a novel synthetic estrogen ligand. Biochem Biophys Res Commun 2003; 312: 656-62.
128. Yamamoto Y, Shibata J, Yonekura K, Sato K, Hashimoto A, Aoyagi Y, et al. TAS-108, a novel oral steroidal antiestrogenic agent, is a pure antagonist on estrogen receptor alpha and a partial agonist on estrogen receptor beta with low uterotrophic effect. Clin Cancer Res 2005; 11: 315-22.
129. Saeki T, Noguchi S, Aogi K, Inaji H, Tabei T, Ikeda T. Evaluation of the safety and tolerability of oral TAS-108 in postmenopausal patients with metastatic breast cancer. Ann Oncol 2009; 20: 868-73.
130. Korach KS. Insights from the study of animals lacking functional estrogen receptor. Science 1994; 266: 1524-7.
131. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor β. Proc Natl Acad Sci USA 1998; 95: 15677-82.
132. Mohler ML, Narayanan R, Coss CC, Hu K, He Y, Wu Z, et al. Estrogen receptor β selective nonsteroidal estrogens: Seeking clinical indications. Expert Opin Ther Pat 2010; 20: 507-34.
133. Dalton, J. T., Miller, D. D., Mohler, M. L., Hong, S.-S., Wu, Z., Srivastava, D. Nuclear receptor binding agents. US20090030036 (2009).
134. Narayanan, R., Yepuru, M., Dalton, J. T. Nuclear receptor binding agents. US20100267767 (2010).
135. Tanabe, M. Peters, R. H., Chao, W.-R., Jong, L. Anti-estrogenic steroids, and associated pharmaceutical compositions and methods of use. US6455517 (2002).
136. Laderoute, K. R., Calaoagan, J. M., Chao, W.-R., Peters, R. H., Hobbs, P. D., Tanabe, M., Amin, K. Method and composition for inhibiting cell proliferation and angiogenesis. US20060264413 (2006).
137. Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, et al. Constitutive activation of Stat3 in human prostate tumors and cell lines: Direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res 2002; 62: 6659-66.
138. Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, et al. ERβ impedes prostate cancer EMT by destabilizing HIF-1α and inhibiting VEGF-mediated snail nuclear localization: Implications for Gleason grading. Cancer Cell 2010; 17: 319-32.
139. Chao WR, Amin K, Shi Y, Hobbs P, Tanabe M, Tanga M, et al. SR16388: A steroidal antiangiogenic agent with potent inhibitory effect on tumor growth in vivo. Angiogenesis 2011; 14: 1-16.
140. Liu MM, Albanese C, Anderson CM, Hilty K, Webb P, Uht RM, et al. Opposing action of estrogen receptors α and β on cyclin D1 gene expression. J Biol Chem 2002; 277: 24353-60.
141. Chang EC, Frasor J, Komm B, Katzenellenbogen BS. Impact of estrogen receptor β on gene networks regulated by estrogen receptor α in breast cancer cells. Endocrinology 2006; 147: 4831-42.
142. Powell E, Xu W. Intermolecular interactions identify ligandselective activity of estrogen receptor α/β dimers. Proc Natl Acad Sci U S A 2008; 105: 19012-7.
143. Rodriguez AL, Tamrazi A, Collins ML, Katzenellenbogen JA. Design, synthesis, and in vitro biological evaluation of small molecule inhibitors of estrogen receptor α coactivator binding. J Med Chem 2004; 47: 600-11.
144. Parent AA, Gunther JR, Katzenellenbogen JA. Blocking estrogen signaling after the hormone: Pyrimidine-core inhibitors of estrogen receptor-coactivator binding. J Med Chem 2008; 51: 6512-30.
145. Gunther JR, Du Y, Rhoden E, Lewis I, Revennaugh B, Moore TW, et al. A set of time-resolved fluorescence resonance energy transfer assays for the discovery of inhibitors of estrogen receptorcoactivator binding. J Biomol Screen 2009; 14: 181-93
146. Fu XD, Simoncini T. Extranuclear signaling of estrogen receptors. IUBMB Life 2008; 60: 502-10.
147. Meegan MJ, Lloyd DG. Advances in the science of estrogen receptor modulation. Curr Med Chem 2003; 10: 181-210.
148. Galluzzo P, Marino M. Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities. Genes Nutr 2006; 1: 161-76.
149. Totta P, Acconcia F, Leone S, Cardillo I, Marino M. Mechanisms of naringenin-induced apoptotic cascade in cancer cells: Involvement of estrogen receptor α and β signalling. IUBMB Life 2004; 56: 491-9.
150. Virgili F, Acconcia F, Ambra R, Rinna A, Totta P, Marino M. Nutritional flavonoids modulate estrogen receptor a signaling. IUBMB Life 2004; 56: 145-51.
151. Bulzomi P, Bolli A, Galluzzo P, Leone S, Acconcia F, Marino M. Naringenin and 17β-estradiol coadministration prevents hormoneinduced human cancer cell growth. IUBMB Life 2010; 62: 51-60.
152. Fitzpatrick JM, Schulman C, Zlotta AR, Schröder FH. Prostate cancer: A serious disease suitable for prevention. BJU Int 2009;103: 864-70.
153. Johns, P. W., Suh, J. D., Daab-krzykowski, A., Mazer, T. B., Mei, F.-I. Process for isolating phytoestrogens from plant protein. US6020471 (2000).
154. Yong, E. L., Yap, S. P. Methods for preparing an estrogenic preparation and isolated estrogenic compounds from a plant and uses thereof. US20030170292 (2003).
155. Kwak, W.-J., Cho, Y.-B., Han, C.-K., Shin, H. J., Ryu, K. H., Yoo, H., Rhee, H. I. Extraction and purification method of active constituents from stem of Lonicera japonica thunb., its usage for antiinflammatory and analgesic drug. US20060014240 (2006).
156. Kelly, G. E. Health supplement. US6987098 (2006).
157. Di Leo, A., Barone, M. Compositions comprising phytoestrogenes selective for estrogen beta receptor and dietary fibres. US20110027230 (2011).
158. Ziegler RG, Hoover RN, Pike MC, Hildesheim A, Nomura AM, West DW, et al. Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 1993; 85: 1819-27.
159. Pietras, R. J., Marquez-garban, D. C. Membrane estrogen receptordirected therapy in breast cancer. US20030044412 (2003).
160. Harrington WR, Kim SH, Funk CC, Madak-Erdogan Z, Schiff R, Katzenellenbogen JA, Katzenellenbogen BS. Estrogen dendrimer conjugates that preferentially activate extranuclear, nongenomic versus genomic pathways of estrogen action. Mol Endocrinol 2006; 20: 491-502.
161. Madak-Erdogan Z, Kieser KJ, Kim SH, Komm B, Katzenellenbogen JA, Katzenellenbogen BS. Nuclear and extranuclear pathway inputs in the regulation of global gene expression by estrogen receptors. Mol Endocrinol 2008; 22: 2116-27.
162. Trogden BG, Kim SH, Lee S, Katzenellenbogen JA. Tethered indoles as functionalizable ligands for the estrogen receptor. Bioorg Med Chem Lett 2009; 19:485-8.
163. Biberger C, von Angerer E. 1-Benzyl-2-phenylindole- and 1,2- diphenylindole-based antiestrogens. Estimation of agonist and antagonist activities in transfection assays. J Steroid Biochem Mol Biol 1998; 64: 277-85.
164. Chambliss KL, Wu Q, Oltmann S, Konaniah ES, Umetani M, Korach KS, et al. Non-nuclear estrogen receptor α signaling promotes cardiovascular protection but no uterine or breast cancer growth in mice. J Clin Invest 2010; 120: 2319-30.
165. McDonnell DP, Dana SL, Hoener PA, Lieberman BA, Imhof MO, Stein RB. Cellular mechanisms which distinguish between hormone- and antihormone-activated estrogen receptor. Ann NY Acad Sci 1995; 761: 121-37.
166. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, et al. Overview of the main outcomes in breast cance prevention trials. Lancet 2003; 361: 296-300.
167. Stenbygaard LE, Herrstedt J, Thomsen JF, Svendsen KR, Engelholm SA, Dombernowsky P. Toremifene and tamoxifen in advanced breast cancer-a double-blind cross-over trial. Breast Cancer Res Treat 1993; 25: 57-63.
168. Lee ES, Schafer JM, Yao K, England G, O'Regan RM, De Los Reyes A, et al. Crossresistance of triphenylethylene-type antiestrogens but not ICI 182,780 in tamoxifenstimulated breast tumors grown in athymic mice. Clin Cancer Res 2000; 6: 4893-9.