ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Blocking Estrogen Signaling After the Hormone: Pyrimidine-Core Inhibitors of Estrogen Receptor-Coactivator Binding

View Author Information
Department of Chemistry, University of Illinois at Urbana−Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801
* To whom correspondence should be addressed. Phone: 217-333-6310. Fax: 217-333-7325. E-mail: [email protected]
Cite this: J. Med. Chem. 2008, 51, 20, 6512–6530
Publication Date (Web):September 12, 2008
https://doi.org/10.1021/jm800698b
Copyright © 2008 American Chemical Society

    Article Views

    2358

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    As an alternative approach to blocking estrogen action, we have developed small molecules that directly disrupt the key estrogen receptor (ER)/coactivator interaction necessary for gene activation. The more direct, protein−protein nature of this disruption might be effective even in hormone-refractory breast cancer. We have synthesized a pyrimidine-core library of moderate size, members of which act as α-helix mimics to block the ERα/coactivator interaction. Structure−activity relationships have been explored with various C-, N-, O-, and S-substituents on the pyrimidine core. Time-resolved fluorescence resonance energy transfer and cell-based reporter gene assays show that the most active members inhibit the ERα/steroid receptor coactivator interaction with Ki′s in the low micromolar range. Through these studies, we have obtained a refined pharmacophore model for activity in this pyrimidine series. Furthermore, the favorable activities of several of these compounds support the feasibility that this coactivator binding inhibition mechanism for blocking estrogen action might provide a potential alternative approach to endocrine therapy.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    See for complete synthetic details, HPLC and CHN analyses, and more extensive biological data, including RBA values. This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 69 publications.

    1. Caitlin M. Tressler and Neal J. Zondlo . Perfluoro-tert-butyl Homoserine Is a Helix-Promoting, Highly Fluorinated, NMR-Sensitive Aliphatic Amino Acid: Detection of the Estrogen Receptor·Coactivator Protein–Protein Interaction by 19F NMR. Biochemistry 2017, 56 (8) , 1062-1074. https://doi.org/10.1021/acs.biochem.6b01020
    2. Jun-Long Zhan, Meng-Wei Wu, Fei Chen, and Bing Han . Cu-Catalyzed [3 + 3] Annulation for the Synthesis of Pyrimidines via β-C(sp3)–H Functionalization of Saturated Ketones. The Journal of Organic Chemistry 2016, 81 (23) , 11994-12000. https://doi.org/10.1021/acs.joc.6b02181
    3. Lech-Gustav Milroy, Tom N. Grossmann, Sven Hennig, Luc Brunsveld, and Christian Ottmann . Modulators of Protein–Protein Interactions. Chemical Reviews 2014, 114 (9) , 4695-4748. https://doi.org/10.1021/cr400698c
    4. Devan Naduthambi, Santosh Bhor, Michael B. Elbaum, and Neal J. Zondlo . Synthesis of a Tetrasubstituted Tetrahydronaphthalene Scaffold for α-Helix Mimicry via a MgBr2-Catalyzed Friedel–Crafts Epoxide Cycloalkylation. Organic Letters 2013, 15 (18) , 4892-4895. https://doi.org/10.1021/ol402334j
    5. Nathan R. Guz, Helena Leuser, and Erick Goldman . Process Development and Multikilogram Syntheses of XL228 Utilizing a Regioselective Isoxazole Formation and a Selective SNAr Reaction to a Pyrimidine Core. Organic Process Research & Development 2013, 17 (8) , 1066-1073. https://doi.org/10.1021/op400137m
    6. Min Shan, Kathryn E. Carlson, Alexander Bujotzek, Anja Wellner, Ronald Gust, Marcus Weber, John A. Katzenellenbogen, and Rainer Haag . Nonsteroidal Bivalent Estrogen Ligands: An Application of the Bivalent Concept to the Estrogen Receptor. ACS Chemical Biology 2013, 8 (4) , 707-715. https://doi.org/10.1021/cb3006243
    7. Sascha Fuchs, Hoang D. Nguyen, Trang T. P. Phan, Matthew F. Burton, Lidia Nieto, Ingrid J. de Vries-van Leeuwen, Andrea Schmidt, Monireh Goodarzifard, Stijn M. Agten, Rolf Rose, Christian Ottmann, Lech-Gustav Milroy, and Luc Brunsveld . Proline Primed Helix Length as a Modulator of the Nuclear Receptor–Coactivator Interaction. Journal of the American Chemical Society 2013, 135 (11) , 4364-4371. https://doi.org/10.1021/ja311748r
    8. Prabodh Sadana, Jong Yeon Hwang, Ramy R. Attia, Leggy A. Arnold, Geoffrey Neale, and R. Kiplin Guy . Similarities and Differences between Two Modes of Antagonism of the Thyroid Hormone Receptor. ACS Chemical Biology 2011, 6 (10) , 1096-1106. https://doi.org/10.1021/cb200092v
    9. Terry W. Moore, Jillian R. Gunther, and John A. Katzenellenbogen. Probing the Topological Tolerance of Multimeric Protein Interactions: Evaluation of an Estrogen/Synthetic Ligand for FK506 Binding Protein Conjugate. Bioconjugate Chemistry 2010, 21 (10) , 1880-1889. https://doi.org/10.1021/bc100266v
    10. Anna B. Williams, Patrick T. Weiser, Robert N. Hanson, Jillian R. Gunther and John A. Katzenellenbogen . Synthesis of Biphenyl Proteomimetics as Estrogen Receptor-α Coactivator Binding Inhibitors. Organic Letters 2009, 11 (23) , 5370-5373. https://doi.org/10.1021/ol901999f
    11. Jillian R. Gunther, Alexander A. Parent and John A. Katzenellenbogen. Alternative Inhibition of Androgen Receptor Signaling: Peptidomimetic Pyrimidines As Direct Androgen Receptor/Coactivator Disruptors. ACS Chemical Biology 2009, 4 (6) , 435-440. https://doi.org/10.1021/cb900043e
    12. Parul Kaushik, Ravinder Kumar, Shiwani Khokhar, Sukhvinder Dhiman, Raj Kamal. Recent Synthetic and Biological Developments on 1,2,4‐Triazolopyrimidines. ChemistrySelect 2023, 8 (33) https://doi.org/10.1002/slct.202301534
    13. Nikolas Hörmann, Christina Kalchschmid, Patricia Grabher, Isabella Grassmayr, Paul Kapitza, Teresa Kaserer, Ronald Gust. Development of heterodimeric estrogen receptor alpha antagonists to target simultaneously the ligand and coactivator binding site. Archiv der Pharmazie 2023, 356 (7) https://doi.org/10.1002/ardp.202200638
    14. Jae Eun Jung, Yunseong Jang, Hee Jin Jeong, Sung Joon Kim, Kichul Park, Do Hee Oh, Ahran Yu, Chan Sun Park, Seo-Jung Han. Discovery of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one and 3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one derivatives as novel ENPP1 inhibitors. Bioorganic & Medicinal Chemistry Letters 2022, 75 , 128947. https://doi.org/10.1016/j.bmcl.2022.128947
    15. Rimpa De, Utsav Sengupta, Antony Savarimuthu, Souvik Misra, Jayanta Nanda, Mrinal K. Bera. A practical and cost-effective approach to polysubstituted pyrimidine derivatives via DBU mediated redox isomerization of propargyl alcohol and subsequent N–C–N fragment condensation. New Journal of Chemistry 2022, 46 (22) , 10603-10610. https://doi.org/10.1039/D2NJ00586G
    16. Sergio C. Chai, Taosheng Chen. Nuclear Receptors. 2022, 151-164. https://doi.org/10.1016/B978-0-12-820472-6.00113-4
    17. Jae Eun Jung, Yunseong Jang, Hee Jin Jeong, Sung Joon Kim, Kichul Park, Do Hee Oh, Chan Sun Park, Seo-jung Han. Discovery of 3,4-Dihydropyrimido[4,5- d]Pyrimidin-2(1 H)-One and 3,4-Dihydropyrido[2,3- d]Pyrimidin-2(1 H)-One Derivatives as Novel ENPP1 Inhibitors. SSRN Electronic Journal 2022, 48 https://doi.org/10.2139/ssrn.4157089
    18. Ming M. Zhang, Zhen Z. Zhan, Meng Wang, He S. Wang, Guo S. Huang. Direct Synthesis of 2,4,6‐Trisubstituted Pyrimidines via Base‐Mediated One‐Pot Multicomponent Reaction. ChemistrySelect 2021, 6 (47) , 13627-13632. https://doi.org/10.1002/slct.202103621
    19. Divya Bafna, Fuqiang Ban, Paul S. Rennie, Kriti Singh, Artem Cherkasov. Computer-Aided Ligand Discovery for Estrogen Receptor Alpha. International Journal of Molecular Sciences 2020, 21 (12) , 4193. https://doi.org/10.3390/ijms21124193
    20. Sergio C. Chai, William C. Wright, Taosheng Chen. Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer. Medicinal Research Reviews 2020, 40 (3) , 1061-1083. https://doi.org/10.1002/med.21648
    21. Jian Shen, Xu Meng. Selective synthesis of pyrimidines from cinnamyl alcohols and amidines using the heterogeneous OMS-2 catalyst. Catalysis Communications 2020, 138 , 105846. https://doi.org/10.1016/j.catcom.2019.105846
    22. André Fischer, Martin Smieško. Allosteric Binding Sites On Nuclear Receptors: Focus On Drug Efficacy and Selectivity. International Journal of Molecular Sciences 2020, 21 (2) , 534. https://doi.org/10.3390/ijms21020534
    23. Raj Kamal, Ravinder Kumar, Vipan Kumar, Vikas Kumar, Kushal K. Bansal, Prabodh C. Sharma. Synthesis, Anthelmintic and Antimicrobial Evaluation of New 2‐Arylidene‐1‐(4‐methyl‐6‐phenylpyrimidin‐2‐yl)hydrazines. ChemistrySelect 2019, 4 (2) , 713-717. https://doi.org/10.1002/slct.201802822
    24. Weirong Qin, Mingsheng Xie, Xuan Qin, Qi Fang, Feng Yin, Zigang Li. Recent advances in peptidomimetics antagonists targeting estrogen receptor α-coactivator interaction in cancer therapy. Bioorganic & Medicinal Chemistry Letters 2018, 28 (17) , 2827-2836. https://doi.org/10.1016/j.bmcl.2018.05.062
    25. Aleksandra Piontek, Elwira Bisz, Michal Szostak. Eisenkatalysierte Kreuzkupplungen in der Synthese von Pharmazeutika: Streben nach Nachhaltigkeit. Angewandte Chemie 2018, 130 (35) , 11284-11297. https://doi.org/10.1002/ange.201800364
    26. Aleksandra Piontek, Elwira Bisz, Michal Szostak. Iron‐Catalyzed Cross‐Couplings in the Synthesis of Pharmaceuticals: In Pursuit of Sustainability. Angewandte Chemie International Edition 2018, 57 (35) , 11116-11128. https://doi.org/10.1002/anie.201800364
    27. Cheng Xu, Shi‐Fen Jiang, Xiao‐Hui Wen, Qin Zhang, Zhi‐Wen Zhou, Yan‐Dong Wu, Feng‐Cheng Jia, An‐Xin Wu. Dimethyl Sulfoxide Serves as a Dual Synthon: Construction of 5‐Methyl Pyrimidine Derivatives via Four Component Oxidative Annulation. Advanced Synthesis & Catalysis 2018, 360 (12) , 2267-2271. https://doi.org/10.1002/adsc.201800180
    28. A. A. Harutyunyan, G. T. Gukasyan, H. A. Panosyan, R. A. Tamazyan, A. G. Aivazyan, G. G. Danagulyan. Synthesis and Structure of New Substituted Pyrimidinone with Unsaturated Side Chain. Russian Journal of Organic Chemistry 2018, 54 (5) , 771-775. https://doi.org/10.1134/S1070428018050160
    29. Huiming Cao, Xun Li, Wenjuan Zhang, Ling Wang, Yu Pan, Zhen Zhou, Minjie Chen, Aiqian Zhang, Yong Liang, Maoyong Song. Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies. Archives of Toxicology 2018, 92 (4) , 1471-1482. https://doi.org/10.1007/s00204-018-2159-2
    30. Julie A Pollock, Suzanne E Wardell, Alexander A Parent, David B Stagg, Stephanie J Ellison, Holly M Alley, Christina A Chao, Scott A Lawrence, James P Stice, Ivan Spasojevic, Jennifer G Baker, Sung Hoon Kim, Donald P McDonnell, John A Katzenellenbogen, John D Norris. Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer. Nature Chemical Biology 2016, 12 (10) , 795-801. https://doi.org/10.1038/nchembio.2131
    31. Dhanaji V. Jawale, Umesh R. Pratap, Manisha R. Bhosale, Ramrao A. Mane. One‐Pot Three‐Component Synthesis of 2‐Amino Pyrimidines in Aqueous PEG‐400 at Ambient Temperature. Journal of Heterocyclic Chemistry 2016, 53 (5) , 1626-1630. https://doi.org/10.1002/jhet.673
    32. Eric Biron, François Bédard. Recent progress in the development of protein–protein interaction inhibitors targeting androgen receptor–coactivator binding in prostate cancer. The Journal of Steroid Biochemistry and Molecular Biology 2016, 161 , 36-44. https://doi.org/10.1016/j.jsbmb.2015.07.006
    33. Kriti Singh, Ravi Shashi Nayana Munuganti, Eric Leblanc, Yu Lun Lin, Euphemia Leung, Nada Lallous, Miriam Butler, Artem Cherkasov, Paul S Rennie. In silico discovery and validation of potent small-molecule inhibitors targeting the activation function 2 site of human oestrogen receptor α. Breast Cancer Research 2015, 17 (1) https://doi.org/10.1186/s13058-015-0529-8
    34. O. V. Smirnova. Competitive agonists and antagonists of steroid nuclear receptors: Evolution of the concept or its reversal. Biochemistry (Moscow) 2015, 80 (10) , 1227-1234. https://doi.org/10.1134/S000629791510003X
    35. T. A. Kuz’menko, L. N. Divaeva, A. S. Morkovnik. 4-substituted 2-chloromethyl[1,2,4]triazolo[1,5-a]benzimidazoles and their transformations. Russian Journal of Organic Chemistry 2015, 51 (10) , 1474-1480. https://doi.org/10.1134/S1070428015100218
    36. Kyle T Helzer, Christopher Hooper, Shigeki Miyamoto, Elaine T Alarid. Ubiquitylation of nuclear receptors: new linkages and therapeutic implications. Journal of Molecular Endocrinology 2015, 54 (3) , R151-R167. https://doi.org/10.1530/JME-14-0308
    37. Terry W. Moore, Jillian R. Gunther, John A. Katzenellenbogen. Estrogen Receptor Alpha/Co-activator Interaction Assay: TR-FRET. 2015, 545-553. https://doi.org/10.1007/978-1-4939-2425-7_36
    38. Silvia Rodriguez-Marin, Natasha S. Murphy, Helena J. Shepherd, Andrew J. Wilson. Design, synthesis and conformational analyses of bifacial benzamide based foldamers. RSC Advances 2015, 5 (126) , 104187-104192. https://doi.org/10.1039/C5RA20451H
    39. Ravi S.N. Munuganti, Mohamed D.H. Hassona, Eric Leblanc, Kate Frewin, Kriti Singh, Dennis Ma, Fuqiang Ban, Michael Hsing, Hans Adomat, Nada Lallous, Christophe Andre, Jon Paul Selvam Jonadass, Amina Zoubeidi, Robert N. Young, Emma Tomlinson Guns, Paul S. Rennie, Artem Cherkasov. Identification of a Potent Antiandrogen that Targets the BF3 Site of the Androgen Receptor and Inhibits Enzalutamide-Resistant Prostate Cancer. Chemistry & Biology 2014, 21 (11) , 1476-1485. https://doi.org/10.1016/j.chembiol.2014.09.012
    40. Arthur Christopoulos, Jean-Pierre Changeux, William A. Catterall, Doriano Fabbro, Thomas P. Burris, John A. Cidlowski, Richard W. Olsen, John A. Peters, Richard R. Neubig, Jean-Philippe Pin, Patrick M. Sexton, Terry P. Kenakin, Frederick J. Ehlert, Michael Spedding, Christopher J. Langmead, . International Union of Basic and Clinical Pharmacology. XC. Multisite Pharmacology: Recommendations for the Nomenclature of Receptor Allosterism and Allosteric Ligands. Pharmacological Reviews 2014, 66 (4) , 918-947. https://doi.org/10.1124/pr.114.008862
    41. John A. Blackford, Kyle R. Brimacombe, Edward J. Dougherty, Madhumita Pradhan, Min Shen, Zhuyin Li, Douglas S. Auld, Carson C. Chow, Christopher P. Austin, S. Stoney Simons. Research Resource: Modulators of Glucocorticoid Receptor Activity Identified by a New High-Throughput Screening Assay. Molecular Endocrinology 2014, 28 (7) , 1194-1206. https://doi.org/10.1210/me.2014-1069
    42. L. M. Sinegovskaya, V. A. Shagun, E. P. Levanova, N. A. Korchevin, I. B. Rozentsveig, V. I. Smirnov. Spectral and Quantum-Chemical Study of Acid-Catalyzed Heterocyclization of S-(2-Chloroprop-2-EN-1-YL)Isothiuronium Chloride with Acetylacetone. Chemistry of Heterocyclic Compounds 2014, 50 (3) , 404-414. https://doi.org/10.1007/s10593-014-1488-1
    43. Kairit Tints, Madis Prink, Toomas Neuman, Kaia Palm. LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells. International Journal of Molecular Sciences 2014, 15 (4) , 5680-5698. https://doi.org/10.3390/ijms15045680
    44. E. P. Levanova, V. A. Grabel’nykh, V. S. Vakhrina, N. V. Russavskaya, A. I. Albanov, N. A. Korchevin, I. B. Rozentsveig. Synthesis of new 2-(alkenylsulfanyl)pyrimidine derivatives. Russian Journal of Organic Chemistry 2014, 50 (3) , 429-433. https://doi.org/10.1134/S1070428014030221
    45. Patrick T. Weiser, Ching-Yi Chang, Donald P. McDonnell, Robert N. Hanson. 4,4′-Unsymmetrically substituted 3,3′-biphenyl alpha helical proteomimetics as potential coactivator binding inhibitors. Bioorganic & Medicinal Chemistry 2014, 22 (2) , 917-926. https://doi.org/10.1016/j.bmc.2013.10.051
    46. Andrew R. Bayly, Andrew J. P. White, Alan C. Spivey. Design and Synthesis of a Prototype Scaffold for Five‐Residue α‐Helix Mimetics. European Journal of Organic Chemistry 2013, 2013 (25) , 5566-5569. https://doi.org/10.1002/ejoc.201300478
    47. Laura Caboni, David G. Lloyd. Beyond the Ligand-Binding Pocket: Targeting Alternate Sites in Nuclear Receptors. Medicinal Research Reviews 2013, 33 (5) , 1081-1118. https://doi.org/10.1002/med.21275
    48. Thomas J. Delia. Grignard Reactions Involving Halogenated Pyrimidines. Journal of Heterocyclic Chemistry 2013, 50 (4) , 735-745. https://doi.org/10.1002/jhet.1543
    49. Marta Dominguez Seoane, Katja Petkau-Milroy, Belen Vaz, Sabine Möcklinghoff, Simon Folkertsma, Lech-Gustav Milroy, Luc Brunsveld. Structure–activity relationship studies of miniproteins targeting the androgen receptor–coactivator interaction. MedChemComm 2013, 4 (1) , 187-192. https://doi.org/10.1039/C2MD20182H
    50. Zhenhuan Zhang, Yunguang Sun, Young-Wook Cho, Carson C. Chow, S. Stoney Simons. PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation. Journal of Biological Chemistry 2013, 288 (1) , 42-58. https://doi.org/10.1074/jbc.M112.427740
    51. Prabodh Sadana. Noncanonical mechanisms to regulate nuclear receptor signaling. Future Medicinal Chemistry 2012, 4 (10) , 1307-1333. https://doi.org/10.4155/fmc.12.72
    52. Smita Awasthi, S. Stoney Simons. Separate regions of glucocorticoid receptor, coactivator TIF2, and comodulator STAMP modify different parameters of glucocorticoid-mediated gene induction. Molecular and Cellular Endocrinology 2012, 355 (1) , 121-134. https://doi.org/10.1016/j.mce.2012.02.001
    53. S. Stoney Simons, Carson C. Chow. The road less traveled: New views of steroid receptor action from the path of dose–response curves. Molecular and Cellular Endocrinology 2012, 348 (2) , 373-382. https://doi.org/10.1016/j.mce.2011.05.030
    54. Hoang D. Nguyen, Trang T. P. Phan, Maelle Carraz, Luc Brunsveld. Estrogen Receptor α/β–cofactor motif interactions; interplay of tyrosine 537/488 phosphorylation and LXXLL motifs. Molecular BioSystems 2012, 8 (12) , 3134. https://doi.org/10.1039/c2mb25257k
    55. Aiming Sun, Terry W. Moore, Jillian R. Gunther, Mi‐Sun Kim, Eric Rhoden, Yuhong Du, Haian Fu, James P. Snyder, John A. Katzenellenbogen. Discovering Small‐Molecule Estrogen Receptor α/Coactivator Binding Inhibitors: High‐Throughput Screening, Ligand Development, and Models for Enhanced Potency. ChemMedChem 2011, 6 (4) , 654-666. https://doi.org/10.1002/cmdc.201000507
    56. Jong Yeon Hwang, Wenwei Huang, Leggy A. Arnold, Ruili Huang, Ramy R. Attia, Michele Connelly, Jennifer Wichterman, Fangyi Zhu, Indre Augustinaite, Christopher P. Austin, James Inglese, Ronald L. Johnson, R. Kiplin Guy. Methylsulfonylnitrobenzoates, a New Class of Irreversible Inhibitors of the Interaction of the Thyroid Hormone Receptor and Its Obligate Coactivators That Functionally Antagonizes Thyroid Hormone. Journal of Biological Chemistry 2011, 286 (14) , 11895-11908. https://doi.org/10.1074/jbc.M110.200436
    57. Kerang Wang, Ling Wu, Zhanbin Qin, Xinhao Yan, Xiaoliu Li, Hua Chen, Pingzhu Zhang, Jinchao Zhang. Synthesis and antitumor activity of novel ribonucleosides with C-5 OH replaced by a diaminopyrimidinyl group. Bioorganic & Medicinal Chemistry Letters 2011, 21 (3) , 916-919. https://doi.org/10.1016/j.bmcl.2010.12.069
    58. David J. Shapiro, Chengjian Mao, Milu T. Cherian. Small Molecule Inhibitors as Probes for Estrogen and Androgen Receptor Action. Journal of Biological Chemistry 2011, 286 (6) , 4043-4048. https://doi.org/10.1074/jbc.R110.203026
    59. Hülya Göksel, Dorothee Wasserberg, Sabine Möcklinghoff, Belen Vaz Araujo, Luc Brunsveld. An on-bead assay for the identification of non-natural peptides targeting the Androgen Receptor–cofactor interaction. Bioorganic & Medicinal Chemistry 2011, 19 (1) , 306-311. https://doi.org/10.1016/j.bmc.2010.11.019
    60. Erin K. Shanle, Wei Xu. Selectively targeting estrogen receptors for cancer treatment. Advanced Drug Delivery Reviews 2010, 62 (13) , 1265-1276. https://doi.org/10.1016/j.addr.2010.08.001
    61. Elaine Y. Hsia, Michael L. Goodson, June X. Zou, Martin L. Privalsky, Hong-Wu Chen. Nuclear receptor coregulators as a new paradigm for therapeutic targeting. Advanced Drug Delivery Reviews 2010, 62 (13) , 1227-1237. https://doi.org/10.1016/j.addr.2010.09.016
    62. Karolien De Bosscher, Ilse M. Beck, Guy Haegeman. Classic glucocorticoids versus non-steroidal glucocorticoid receptor modulators: Survival of the fittest regulator of the immune system?. Brain, Behavior, and Immunity 2010, 24 (7) , 1035-1042. https://doi.org/10.1016/j.bbi.2010.06.010
    63. Angela N Koehler. A complex task? Direct modulation of transcription factors with small molecules. Current Opinion in Chemical Biology 2010, 14 (3) , 331-340. https://doi.org/10.1016/j.cbpa.2010.03.022
    64. Terry W. Moore, Christopher G. Mayne, John A. Katzenellenbogen. Minireview: Not Picking Pockets: Nuclear Receptor Alternate-Site Modulators (NRAMs). Molecular Endocrinology 2010, 24 (4) , 683-695. https://doi.org/10.1210/me.2009-0362
    65. Yusuke Mita, Kosuke Dodo, Tomomi Noguchi-Yachide, Hiroyuki Miyachi, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa. LXXLL peptide mimetics as inhibitors of the interaction of vitamin D receptor with coactivators. Bioorganic & Medicinal Chemistry Letters 2010, 20 (5) , 1712-1717. https://doi.org/10.1016/j.bmcl.2010.01.079
    66. Trang Phan, Hoang D. Nguyen, Hülya Göksel, Sabine Möcklinghoff, Luc Brunsveld. Phage display selection of miniprotein binders of the Estrogen Receptor. Chemical Communications 2010, 46 (43) , 8207. https://doi.org/10.1039/c0cc02727h
    67. Gerd Wohlfahrt, Julius Sipilä, Lars‐Olof Pietilä. Field‐based comparison of ligand and coactivator binding sites of nuclear receptors. Biopolymers 2009, 91 (10) , 884-894. https://doi.org/10.1002/bip.21273
    68. Maëlle Carraz, Wilbert Zwart, Trang Phan, Rob Michalides, Luc Brunsveld. Perturbation of Estrogen Receptor α Localization with Synthetic Nona-Arginine LXXLL-Peptide Coactivator Binding Inhibitors. Chemistry & Biology 2009, 16 (7) , 702-711. https://doi.org/10.1016/j.chembiol.2009.06.009
    69. Terry W. Moore, John A. Katzenellenbogen. Chapter 21 Inhibitors of Nuclear Hormone Receptor/Coactivator Interactions. 2009, 443-457. https://doi.org/10.1016/S0065-7743(09)04421-2

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect