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

Rational Design and Synthesis of a Novel Thyroid Hormone Antagonist That Blocks Coactivator Recruitment

View Author Information
Program in Chemistry and Chemical Biology, Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143-0446, and Metabolic Research Unit, University of California, San Francisco, California 94143-0540
Cite this: J. Med. Chem. 2002, 45, 15, 3310–3320
Publication Date (Web):June 19, 2002
Copyright © 2002 American Chemical Society

    Article Views





    Other access options


    Abstract Image

    Recent efforts have focused on the design and synthesis of thyroid hormone (T3) antagonists as potential therapeutic agents and chemical probes to understand hormone-signaling pathways. We previously reported the development of novel first-generation T3 antagonists DIBRT, HY-4, and GC-14 using the “extension hypothesis” as a general guideline in hormone antagonist design. 1-3 These compounds contain extensions at the 5‘-position (DIBRT, GC-14) of the outer thyronine ring or from the bridging carbon (HY-4). All of these compounds have only a modest affinity and potency for the thyroid hormone receptor (TR) that limits studies of their antagonistic actions. Here, we report the design and synthesis of a novel series of 5‘-phenylethynyl derivatives sharing the GC-1 halogen-free thyronine scaffold. 4 One compound (NH-3) is a T3 antagonist with negligible TR agonist activity and improved TR binding affinity and potency that allow for further characterization of its observed activity. One mechanism for antagonism appears to be the ability of NH-3 to block TR−coactivator interactions. NH-3 will be a useful pharmacological tool for further study of T3 signaling and TR function.

    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.


    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.

     Program in Chemistry and Chemical Biology.

     Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology.


     Metabolic Research Unit.


     To whom correspondence should be addressed. Phone:  (415) 476-3620. Fax:  (415) 502-7220. E-mail:  [email protected].

    Cited By

    This article is cited by 89 publications.

    1. Latika Singh, Brandon Pressly, Brenda J. Mengeling, James C. Fettinger, J. David Furlow, Pamela J. Lein, Heike Wulff, and Vikrant Singh . Chasing the Elusive Benzofuran Impurity of the THR Antagonist NH-3: Synthesis, Isotope Labeling, and Biological Activity. The Journal of Organic Chemistry 2016, 81 (5) , 1870-1876.
    2. Amit A. Joharapurkar, Vipin V. Dhote, and Mukul R. Jain . Selective Thyromimetics Using Receptor and Tissue Selectivity Approaches: Prospects for Dyslipidemia. Journal of Medicinal Chemistry 2012, 55 (12) , 5649-5675.
    3. Jong Yeon Hwang, Ramy R. Attia, Fangyi Zhu, Lei Yang, Andrew Lemoff, Cynthia Jeffries, Michele C. Connelly, and R. Kiplin Guy . Synthesis and Evaluation of Sulfonylnitrophenylthiazoles (SNPTs) as Thyroid Hormone Receptor–Coactivator Interaction Inhibitors. Journal of Medicinal Chemistry 2012, 55 (5) , 2301-2310.
    4. 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.
    5. Jong Yeon Hwang, Leggy A. Arnold, Fangyi Zhu, Aaron Kosinski, Thomas J. Mangano, Vincent Setola, Bryan L. Roth and R. Kiplin Guy. Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors. Journal of Medicinal Chemistry 2009, 52 (13) , 3892-3901.
    6. M. Jeyakumar, Paul Webb, John D. Baxter, Thomas S. Scanlan and John A. Katzenellenbogen . Quantification of Ligand-Regulated Nuclear Receptor Corepressor and Coactivator Binding, Key Interactions Determining Ligand Potency and Efficacy for the Thyroid Hormone Receptor. Biochemistry 2008, 47 (28) , 7465-7476.
    7. Jianfei Zheng, Atsushi Hashimoto, Marc Putnam, Katherine Miller and John T. Koh . Development of a Thyroid Hormone Receptor Targeting Conjugate. Bioconjugate Chemistry 2008, 19 (6) , 1227-1234.
    8. Konrad Koehler,, Sandra Gordon,, Peter Brandt,, Bo Carlsson,, Anna Bäcksbro-Saeidi,, Theresa Apelqvist,, Peter Agback,, Gary J. Grover,, William Nelson,, Marlena Grynfarb,, Mathias Färnegårdh,, Stefan Rehnmark, and, Johan Malm. Thyroid Receptor Ligands. 6. A High Affinity “Direct Antagonist” Selective for the Thyroid Hormone Receptor. Journal of Medicinal Chemistry 2006, 49 (23) , 6635-6637.
    9. Cory A. Ocasio and Thomas S. Scanlan. Design and Characterization of a Thyroid Hormone Receptor α (TRα)-Specific Agonist. ACS Chemical Biology 2006, 1 (9) , 585-593.
    10. Åsa Hedfors,, Theresa Appelqvist,, Bo Carlsson,, Lars-Göran Bladh,, Chris Litten,, Peter Agback,, Marlena Grynfarb,, Konrad F. Koehler, and, Johan Malm. Thyroid Receptor Ligands. 3. Design and Synthesis of 3,5-Dihalo-4-alkoxyphenylalkanoic Acids as Indirect Antagonists of the Thyroid Hormone Receptor. Journal of Medicinal Chemistry 2005, 48 (9) , 3114-3117.
    11. Ngoc-Ha Nguyen,, James W. Apriletti,, John D. Baxter, and, Thomas S. Scanlan. Hammett Analysis of Selective Thyroid Hormone Receptor Modulators Reveals Structural and Electronic Requirements for Hormone Antagonists. Journal of the American Chemical Society 2005, 127 (13) , 4599-4608.
    12. Hikari A. I. Yoshihara,, James W. Apriletti,, John D. Baxter, and, Thomas S. Scanlan. Structural Determinants of Selective Thyromimetics. Journal of Medicinal Chemistry 2003, 46 (14) , 3152-3161.
    13. Jason K. B. Nguyen, Patsy Gómez‐Picos, Yiwen Liu, Katie Ovens, B. Frank Eames. Common features of cartilage maturation are not conserved in an amphibian model. Developmental Dynamics 2023, 252 (11) , 1375-1390.
    14. Katharina Koch, Kristina Bartmann, Julia Hartmann, Julia Kapr, Jördis Klose, Eliška Kuchovská, Melanie Pahl, Kevin Schlüppmann, Etta Zühr, Ellen Fritsche. Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation. Frontiers in Toxicology 2022, 4
    15. Skylar J. Ferrara, Priya Chaudhary, Margaret J. DeBell, Gail Marracci, Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier, Ben Emery, Dennis Bourdette, Thomas S. Scanlan. TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor. Cell Chemical Biology 2022, 29 (2) , 239-248.e4.
    16. Yanis Zekri, Laure Dall Agnol, Frédéric Flamant, Romain Guyot. In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors. iScience 2021, 24 (9) , 102957.
    17. Kyla M. Walter, Latika Singh, Vikrant Singh, Pamela J. Lein. Investigation of NH3 as a selective thyroid hormone receptor modulator in larval zebrafish (Danio rerio). NeuroToxicology 2021, 84 , 96-104.
    18. Iván Lazcano, Gabriela Hernández-Puga, Juan Pablo Robles, Aurea Orozco. Alternative ligands for thyroid hormone receptors. Molecular and Cellular Endocrinology 2019, 493 , 110448.
    19. Kentaro Hirose, Alexander Y. Payumo, Stephen Cutie, Alison Hoang, Hao Zhang, Romain Guyot, Dominic Lunn, Rachel B. Bigley, Hongyao Yu, Jiajia Wang, Megan Smith, Ellen Gillett, Sandra E. Muroy, Tobias Schmid, Emily Wilson, Kenneth A. Field, DeeAnn M. Reeder, Malcom Maden, Michael M. Yartsev, Michael J. Wolfgang, Frank Grützner, Thomas S. Scanlan, Luke I. Szweda, Rochelle Buffenstein, Guang Hu, Frederic Flamant, Jeffrey E. Olgin, Guo N. Huang. Evidence for hormonal control of heart regenerative capacity during endothermy acquisition. Science 2019, 364 (6436) , 184-188.
    20. Natasha N. Chattergoon, Samantha Louey, Thomas Scanlan, Isa Lindgren, George D. Giraud, Kent L. Thornburg. Thyroid hormone receptor function in maturing ovine cardiomyocytes. The Journal of Physiology 2019, 597 (8) , 2163-2176.
    21. Veerle M. Darras. The Role of Maternal Thyroid Hormones in Avian Embryonic Development. Frontiers in Endocrinology 2019, 10
    22. Déborah Harrus, Hélène Déméné, Edwin Vasquez, Abdelhay Boulahtouf, Pierre Germain, Ana Carolina Figueira, Martin L. Privalsky, William Bourguet, Albane le Maire. Pathological Interactions Between Mutant Thyroid Hormone Receptors and Corepressors and Their Modulation by a Thyroid Hormone Analogue with Therapeutic Potential. Thyroid 2018, 28 (12) , 1708-1722.
    23. Louise S. Mackenzie. Thyroid Hormone Receptor Antagonists: From Environmental Pollution to Novel Small Molecules. 2018, 147-162.
    24. Brenda J. Mengeling, Yuzhu Wei, Lucia N. Dobrawa, Mischa Streekstra, Jochem Louisse, Vikrant Singh, Latika Singh, Pamela J. Lein, Heike Wulff, Albertinka J. Murk, J. David Furlow. A multi-tiered, in vivo, quantitative assay suite for environmental disruptors of thyroid hormone signaling. Aquatic Toxicology 2017, 190 , 1-10.
    25. Hongwei Ma, Fan Yang, Michael R. Butler, Joshua Belcher, T. Michael Redmond, Andrew T. Placzek, Thomas S. Scanlan, Xi‐Qin Ding. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. The FASEB Journal 2017, 31 (8) , 3425-3438.
    26. Frédéric Flamant, Karine Gauthier, Sabine Richard. Genetic Investigation of Thyroid Hormone Receptor Function in the Developing and Adult Brain. 2017, 303-335.
    27. Odile J. Bronchain, Albert Chesneau, Anne-Hélène Monsoro-Burq, Pascale Jolivet, Elodie Paillard, Thomas S. Scanlan, Barbara A. Demeneix, Laurent M. Sachs, Nicolas Pollet. Implication of thyroid hormone signaling in neural crest cells migration: Evidence from thyroid hormone receptor beta knockdown and NH3 antagonist studies. Molecular and Cellular Endocrinology 2017, 439 , 233-246.
    28. Fang-Fang Wang, Wei Yang, Yong-Hui Shi, Xiang-Rong Cheng, Guo-Wei Le. Structure-based approach for the study of thyroid hormone receptor binding affinity and subtype selectivity. Journal of Biomolecular Structure and Dynamics 2016, 34 (10) , 2251-2267.
    29. Andrew T. Placzek, Thomas S. Scanlan. New synthetic routes to thyroid hormone analogs: d6-sobetirome, 3H-sobetirome, and the antagonist NH-3. Tetrahedron 2015, 71 (35) , 5946-5951.
    30. 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.
    31. Lori A. Manzon, John H. Youson, Guillaume Holzer, Leopoldo Staiano, Vincent Laudet, Richard G. Manzon. Thyroid hormone and retinoid X receptor function and expression during sea lamprey (Petromyzon marinus) metamorphosis. General and Comparative Endocrinology 2014, 204 , 211-222.
    32. Changhua Shi, Qing Meng, David W Wood. Analysis of the roles of mutations in thyroid hormone receptor-β by a bacterial biosensor system. Journal of Molecular Endocrinology 2014, 52 (1) , 55-66.
    33. Antonio C. Bianco, Grant Anderson, Douglas Forrest, Valerie Anne Galton, Balázs Gereben, Brian W. Kim, Peter A. Kopp, Xiao Hui Liao, Maria Jesus Obregon, Robin P. Peeters, Samuel Refetoff, David S. Sharlin, Warner S. Simonides, Roy E. Weiss, Graham R. Williams. American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models. Thyroid 2014, 24 (1) , 88-168.
    34. Stephen P.H. Alexander, Helen E. Benson, Elena Faccenda, Adam J. Pawson, Joanna L. Sharman, Michael Spedding, John A. Peters, Anthony J. Harmar, . The Concise Guide to PHARMACOLOGY 2013/14: Nuclear Hormone Receptors. British Journal of Pharmacology 2013, 170 (8) , 1652-1675.
    35. Sunitha Meruvu, Stephen D. Ayers, Glenn Winnier, Paul Webb. Thyroid Hormone Analogues: Where Do We Stand in 2013?. Thyroid 2013, 23 (11) , 1333-1344.
    36. AlberTinka J. Murk, Eddy Rijntjes, Bas J. Blaauboer, Rebecca Clewell, Kevin M. Crofton, Milou M.L. Dingemans, J. David Furlow, Robert Kavlock, Josef Köhrle, Robert Opitz, Theo Traas, Theo J. Visser, Menghang Xia, Arno C. Gutleb. Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals. Toxicology in Vitro 2013, 27 (4) , 1320-1346.
    37. Jong Yeon Hwang, Ramy R. Attia, Angela K. Carrillo, Michele C. Connelly, R. Kiplin Guy. Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor–coactivator interaction. Bioorganic & Medicinal Chemistry Letters 2013, 23 (6) , 1891-1895.
    38. J. B. Fini, S. Le Mével, K. Palmier, V. M. Darras, I. Punzon, S. J. Richardson, M. S. Clerget-Froidevaux, B. A. Demeneix. Thyroid Hormone Signaling in the Xenopus laevis Embryo Is Functional and Susceptible to Endocrine Disruption. Endocrinology 2012, 153 (10) , 5068-5081.
    39. Maya Lévy-Bimbot, Geneviève Major, Delphine Courilleau, Jean-Paul Blondeau, Yves Lévi. Tetrabromobisphenol-A disrupts thyroid hormone receptor alpha function in vitro: Use of fluorescence polarization to assay corepressor and coactivator peptide binding. Chemosphere 2012, 87 (7) , 782-788.
    40. R. Thomas Zoeller. Neuroendocrine Regulation of Development, Growth and Metabolism – Thyroid. 2012, 259-270.
    41. Izabela Gierach, Jingjing Li, Wan-Yi Wu, Gary J. Grover, David W. Wood. Bacterial biosensors for screening isoform‐selective ligands for human thyroid receptors α‐1 and β‐1. FEBS Open Bio 2012, 2 (1) , 247-253.
    42. SPH Alexander, A Mathie, JA Peters. NUCLEAR RECEPTORS. British Journal of Pharmacology 2011, 164 (s1)
    43. 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.
    44. A. C. M. Figueira, D. M. Saidemberg, P. C. T. Souza, L. Martínez, T. S. Scanlan, J. D. Baxter, M. S. Skaf, M. S. Palma, P. Webb, I. Polikarpov. Analysis of Agonist and Antagonist Effects on Thyroid Hormone Receptor Conformation by Hydrogen/Deuterium Exchange. Molecular Endocrinology 2011, 25 (1) , 15-31.
    45. M. S. Chernov’yants, A. O. Dolinkin. Heteroaromatic thioamides: Structure and stability of charge transfer complexes with iodine, antithyroid activity. Journal of Structural Chemistry 2010, 51 (6) , 1176-1190.
    46. Alexandre Suman de Araujo, Leandro Martínez, Ricardo de Paula Nicoluci, Munir S. Skaf, Igor Polikarpov. Structural modeling of high-affinity thyroid receptor–ligand complexes. European Biophysics Journal 2010, 39 (11) , 1523-1536.
    47. Johan Malm, Gary J. Grover. Thyroid Hormones and Thyromimetics. 2010, 189-238.
    48. M. S. Chernov’yants, N. V. Aleshina, Z. A. Starikova, E. N. Sul’zhenko. Reaction of 5-methyl-1,3,4-thiadiazoline-2-thione with molecular iodine. Russian Chemical Bulletin 2010, 59 (9) , 1797-1802.
    49. 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.
    50. Timm Schreiber, Kathrin Gassmann, Christine Götz, Ulrike Hübenthal, Michaela Moors, Guido Krause, Hans F. Merk, Ngoc-Ha Nguyen, Thomas S. Scanlan, Josef Abel, Christine R. Rose, Ellen Fritsche. Polybrominated Diphenyl Ethers Induce Developmental Neurotoxicity in a Human in Vitro Model: Evidence for Endocrine Disruption. Environmental Health Perspectives 2010, 118 (4) , 572-578.
    51. Thomas S. Scanlan. Sobetirome: a case history of bench-to-clinic drug discovery and development. Heart Failure Reviews 2010, 15 (2) , 177-182.
    52. Tomoya Hirano, Hiroyuki Kagechika. Thyromimetics: a review of recent reports and patents (2004 – 2009). Expert Opinion on Therapeutic Patents 2010, 20 (2) , 213-228.
    53. Suzana T. Cunha Lima, Ngoc-Ha Nguyen, Marie Togashi, James W. Apriletti, Phuong Nguyen, Igor Polikarpov, Thomas S. Scanlan, John D. Baxter, Paul Webb. Differential effects of TR ligands on hormone dissociation rates: Evidence for multiple ligand entry/exit pathways. The Journal of Steroid Biochemistry and Molecular Biology 2009, 117 (4-5) , 125-131.
    54. . NUCLEAR RECEPTORS. British Journal of Pharmacology 2009
    55. . Thyroid hormone. British Journal of Pharmacology 2009, S166-S166.
    56. M. Jeyakumar, John A. Katzenellenbogen. A dual-acceptor time-resolved Föster resonance energy transfer assay for simultaneous determination of thyroid hormone regulation of corepressor and coactivator binding to the thyroid hormone receptor: Mimicking the cellular context of thyroid hormone action. Analytical Biochemistry 2009, 386 (1) , 73-78.
    57. Napoleão F. Valadares, Igor Polikarpov, Richard C. Garratt. Ligand induced interaction of thyroid hormone receptor beta with its coregulators. The Journal of Steroid Biochemistry and Molecular Biology 2008, 112 (4-5) , 205-212.
    58. Vanya Shah, Phuong Nguyen, Ngoc-Ha Nguyen, Marie Togashi, Thomas S. Scanlan, John D. Baxter, Paul Webb. Complex actions of thyroid hormone receptor antagonist NH-3 on gene promoters in different cell lines. Molecular and Cellular Endocrinology 2008, 296 (1-2) , 69-77.
    59. Mathilde Paris, Vincent Laudet. The history of a developmental stage: Metamorphosis in chordates. genesis 2008, 46 (11) , 657-672.
    60. Juan Du, Jin Qin, Huanxiang Liu, Xiaojun Yao. 3D-QSAR and molecular docking studies of selective agonists for the thyroid hormone receptor β. Journal of Molecular Graphics and Modelling 2008, 27 (2) , 95-104.
    61. Peter Kolkhof, Lars Bärfacker, Alexander Hillisch, Helmut Haning, Stefan Schäfer. Nuclear Receptors as Targets in Cardiovascular Diseases. 2008, 409-429.
    62. Mathilde Paris, Hector Escriva, Michael Schubert, Frédéric Brunet, Julius Brtko, Fabrice Ciesielski, Dominique Roecklin, Valérie Vivat-Hannah, Emilien L. Jamin, Jean-Pierre Cravedi, Thomas S. Scanlan, Jean-Paul Renaud, Nicholas D. Holland, Vincent Laudet. Amphioxus Postembryonic Development Reveals the Homology of Chordate Metamorphosis. Current Biology 2008, 18 (11) , 825-830.
    63. Gabriela Brenta, Sara Danzi, Irwin Klein. Potential therapeutic applications of thyroid hormone analogs. Nature Clinical Practice Endocrinology & Metabolism 2007, 3 (9) , 632-640.
    64. Joseph Chapo, Yanyu Peng, Kelly R. Pitts. A phosphorimager-based filter binding thyroid hormone receptor competition assay for chemical screening. Journal of Pharmacological and Toxicological Methods 2007, 56 (1) , 28-33.
    65. Gary J. Grover, Celeste Dunn, Ngoc-Ha Nguyen, Jamie Boulet, Gao Dong, Jason Domogauer, Peter Barbounis, Thomas S. Scanlan. Pharmacological Profile of the Thyroid Hormone Receptor Antagonist NH3 in Rats. Journal of Pharmacology and Experimental Therapeutics 2007, 322 (1) , 385-390.
    66. Takuma Komatsu, Tomoya Hirano, Chalermkiat Songkram, Emiko Kawachi, Hiroyuki Kagechika. Novel thyroid hormone receptor antagonists with an N-alkylated diphenylamine skeleton. Bioorganic & Medicinal Chemistry 2007, 15 (9) , 3115-3126.
    67. Johan Malm, Sandra Gordon, Peter Brandt, Bo Carlsson, Peter Agback, Anna Bäckbro Saeidi, Johnny Sandberg. Thyroid receptor ligands. Part 7: Indirect antagonists of the thyroid hormone receptor with improved affinity. Bioorganic & Medicinal Chemistry Letters 2007, 17 (7) , 2018-2021.
    68. R. Thomas Zoeller, Shirlee W. Tan, Rochelle W. Tyl. General Background on the Hypothalamic-Pituitary-Thyroid (HPT) Axis. Critical Reviews in Toxicology 2007, 37 (1-2) , 11-53.
    69. Frédéric Flamant, John D. Baxter, Douglas Forrest, Samuel Refetoff, Herbert Samuels, Tom S. Scanlan, Bjorn Vennström, Jacques Samarut. International Union of Pharmacology. LIX. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Thyroid Hormone Receptors. Pharmacological Reviews 2006, 58 (4) , 705-711.
    70. Emmanuelle Havis, Sébastien Le Mevel, Ghislaine Morvan Dubois, De-Li Shi, Thomas S Scanlan, Barbara A Demeneix, Laurent M Sachs. Unliganded thyroid hormone receptor is essential for Xenopus laevis eye development. The EMBO Journal 2006, 25 (20) , 4943-4951.
    71. Yukio Hiroi, Hyung-Hwan Kim, Hao Ying, Fumihiko Furuya, Zhihong Huang, Tommaso Simoncini, Kensuke Noma, Kojiro Ueki, Ngoc-Ha Nguyen, Thomas S. Scanlan, Michael A. Moskowitz, Sheue-Yann Cheng, James K. Liao. Rapid nongenomic actions of thyroid hormone. Proceedings of the National Academy of Sciences 2006, 103 (38) , 14104-14109.
    72. Donald T Elmore. Peptide Synthesis. 2006, 74-128.
    73. Robert Opitz, Ilka Lutz, Ngoc-Ha Nguyen, Thomas S. Scanlan, Werner Kloas. Analysis of thyroid hormone receptor βA mRNA expression in Xenopus laevis tadpoles as a means to detect agonism and antagonism of thyroid hormone action. Toxicology and Applied Pharmacology 2006, 212 (1) , 1-13.
    74. J. David Furlow, Eric S. Neff. A developmental switch induced by thyroid hormone: Xenopus laevis metamorphosis. Trends in Endocrinology & Metabolism 2006, 17 (2) , 40-47.
    75. Cory A Ocasio, Thomas S Scanlan. Clinical prospects for new thyroid hormone analogues. Current Opinion in Endocrinology & Diabetes 2005, 12 (5) , 363-370.
    76. Leandro Martínez, Milton T. Sonoda, Paul Webb, John D. Baxter, Munir S. Skaf, Igor Polikarpov. Molecular Dynamics Simulations Reveal Multiple Pathways of Ligand Dissociation from Thyroid Hormone Receptors. Biophysical Journal 2005, 89 (3) , 2011-2023.
    77. Ellen Fritsche, Jason E. Cline, Ngoc-Ha Nguyen, Thomas S. Scanlan, Josef Abel. Polychlorinated Biphenyls Disturb Differentiation of Normal Human Neural Progenitor Cells: Clue for Involvement of Thyroid Hormone Receptors. Environmental Health Perspectives 2005, 113 (7) , 871-876.
    78. Marie Togashi, Sabine Borngraeber, Ben Sandler, Robert J. Fletterick, Paul Webb, John D. Baxter. Conformational adaptation of nuclear receptor ligand binding domains to agonists: Potential for novel approaches to ligand design. The Journal of Steroid Biochemistry and Molecular Biology 2005, 93 (2-5) , 127-137.
    79. Ben Sandler, Paul Webb, James W. Apriletti, B. Russell Huber, Marie Togashi, Suzana T. Cunha Lima, Sanja Juric, Stefan Nilsson, Richard Wagner, Robert J. Fletterick, John D. Baxter. Thyroxine-Thyroid Hormone Receptor Interactions. Journal of Biological Chemistry 2004, 279 (53) , 55801-55808.
    80. Johan Malm. Therapeutic thyroid hormone ligand patents 1998 – 2003. Expert Opinion on Therapeutic Patents 2004, 14 (8) , 1169-1183.
    81. Jon J. Hangeland, Arthur M. Doweyko, Tamara Dejneka, Todd J. Friends, Pratik Devasthale, Karin Mellström, Johnny Sandberg, Marlena Grynfarb, John S. Sack, Howard Einspahr, Mathias Färnegårdh, Bolette Husman, Jan Ljunggren, Konrad Koehler, Cheryl Sheppard, Johan Malm, Denis E. Ryono. Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta. Bioorganic & Medicinal Chemistry Letters 2004, 14 (13) , 3549-3553.
    82. Jamie M.R. Moore, Sarah J. Galicia, Andrea C. McReynolds, Ngoc-Ha Nguyen, Thomas S. Scanlan, R. Kiplin Guy. Quantitative Proteomics of the Thyroid Hormone Receptor-Coregulator Interactions. Journal of Biological Chemistry 2004, 279 (26) , 27584-27590.
    83. Paul Webb. Selective activators of thyroid hormone receptors. Expert Opinion on Investigational Drugs 2004, 13 (5) , 489-500.
    84. John D Baxter, John W Funder, James W Apriletti, Paul Webb. Towards selectively modulating mineralocorticoid receptor function: lessons from other systems. Molecular and Cellular Endocrinology 2004, 217 (1-2) , 151-165.
    85. John T. Koh. Making virtual screening a reality. Proceedings of the National Academy of Sciences 2003, 100 (12) , 6902-6903.
    86. Paul Webb, Phuong Nguyen, Peter J. Kushner. Differential SERM Effects on Corepressor Binding Dictate ERα Activity in Vivo. Journal of Biological Chemistry 2003, 278 (9) , 6912-6920.
    87. Hikari A.I. Yoshihara, Ngoc-Ha Nguyen, Thomas S. Scanlan. Design and Synthesis of Receptor Ligands. 2003, 71-91.
    88. Paul Webb, Ngoc-Ha Nguyen, Grazia Chiellini, Hikari A.I. Yoshihara, Suzana T. Cunha Lima, James W. Apriletti, Ralff C.J. Ribeiro, Adhirai Marimuthu, Brian L. West, Patrick Goede, Karin Mellstrom, Stefan Nilsson, Peter J. Kushner, Robert J. Fletterick, Thomas S. Scanlan, John D. Baxter. Design of thyroid hormone receptor antagonists from first principles. The Journal of Steroid Biochemistry and Molecular Biology 2002, 83 (1-5) , 59-73.
    89. Wayland Lim, Ngoc-Ha Nguyen, Ha Yung Yang, Thomas S. Scanlan, J. David Furlow. A Thyroid Hormone Antagonist That Inhibits Thyroid Hormone Action in Vivo. Journal of Biological Chemistry 2002, 277 (38) , 35664-35670.

    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.

    Your Mendeley pairing has expired. Please reconnect