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X-ray Crystal Structure of the Novel Enhanced-Affinity Glucocorticoid Agonist Fluticasone Furoate in the Glucocorticoid Receptor−Ligand Binding Domain

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Departments of Computational Chemistry and Medicinal Chemistry, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, U.K., and Departments of Computational Chemistry and Structural Biology, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709
⊥The structure of the fluticasone furoate glucocorticoid receptor–ligand binding domain complex has been deposited in the Brookhaven Protein Data Bank (PDB code 3CLD).
* To whom correspondence should be addressed. Phone: (+44)1438 763651.  Fax: (+44)1438 768302. E-mail: [email protected]
†Department of Medicinal Chemistry, Stevenage.
§Department of Structural Biology, NC.
‡Department of Computational Chemistry, Stevenage.
#Department of Computational Chemistry, NC.
Cite this: J. Med. Chem. 2008, 51, 12, 3349–3352
Publication Date (Web):June 4, 2008
https://doi.org/10.1021/jm800279t
Copyright © 2008 American Chemical Society

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    Abstract

    Abstract Image

    An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone propionate shows the 17α furoate ester to occupy more fully the lipophilic 17α pocket on the receptor, which may account for the enhanced glucocorticoid receptor binding of FF.

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    13. Adrian Hobson. Metabolically Inactivated Glucocorticoids. 2023, 25-36. https://doi.org/10.1007/978-3-031-28732-9_3
    14. Reyhan Metin, Ebru Demet Akten. Drug repositioning to propose alternative modulators for glucocorticoid receptor through structure-based virtual screening. Journal of Biomolecular Structure and Dynamics 2022, 40 (21) , 11418-11433. https://doi.org/10.1080/07391102.2021.1960608
    15. Savannah M. Rocha, Anna C. Fagre, Amanda S. Latham, Jason E. Cummings, Tawfik A. Aboellail, Philip Reigan, Devin A. Aldaz, Casey P. McDermott, Katriana A. Popichak, Rebekah C. Kading, Tony Schountz, Neil D. Theise, Richard A. Slayden, Ronald B. Tjalkens. A Novel Glucocorticoid and Androgen Receptor Modulator Reduces Viral Entry and Innate Immune Inflammatory Responses in the Syrian Hamster Model of SARS-CoV-2 Infection. Frontiers in Immunology 2022, 13 https://doi.org/10.3389/fimmu.2022.811430
    16. Steven Timmermans, Jolien Vandewalle, Claude Libert. Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer. Cells 2022, 11 (4) , 683. https://doi.org/10.3390/cells11040683
    17. Sandra Anderson, Paul Atkins, Per Bäckman, David Cipolla, Andrew Clark, Evangelia Daviskas, Bernd Disse, Plamena Entcheva-Dimitrov, Rick Fuller, Igor Gonda, Hans Lundbäck, Bo Olsson, Jeffry Weers, . Inhaled Medicines: Past, Present, and Future. Pharmacological Reviews 2022, 74 (1) , 48-118. https://doi.org/10.1124/pharmrev.120.000108
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    19. A. I. Sinopalnikov. Combined therapy with inhaled glucocorticosteroids and long-acting β2-agonists in patients with bronchial asthma: the problem of choice. Meditsinskiy sovet = Medical Council 2021, (16) , 52-59. https://doi.org/10.21518/2079-701X-2021-16-52-59
    20. Mitchell A. Avery, Amar G. Chittiboyina. Anti‐Inflammatory Glucocorticoids. 2021, 1-125. https://doi.org/10.1002/0471266949.bmc192.pub2
    21. Britta Bonn, Matthew Perry. The API. 2021, 13-34. https://doi.org/10.1016/B978-0-12-814974-4.00006-7
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    25. Ann Louw. GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life. Frontiers in Immunology 2019, 10 https://doi.org/10.3389/fimmu.2019.01693
    26. Emma D. Deeks, Katherine A. Lyseng-Williamson, Yahiya Y. Syed. Fluticasone furoate/vilanterol dry-powder inhaler in asthma: a guide to its use in the EU. Drugs & Therapy Perspectives 2017, 33 (4) , 153-159. https://doi.org/10.1007/s40267-017-0392-z
    27. P. Sjö, T. Hansson, K. Edman. The Discovery of Potent and Selective Nonsteroidal Glucocorticoid Receptor Modulators AZD5423 and AZD7594, for the Inhaled Treatment of Respiratory Diseases. 2017, 450-487. https://doi.org/10.1016/B978-0-12-409547-2.12466-7
    28. Martin Hemmerling, Karl Edman, Matti Lepistö, Anders Eriksson, Svetlana Ivanova, Jan Dahmén, Hartmut Rehwinkel, Markus Berger, Ramon Hendrickx, Matthew Dearman, Tina Jellesmark Jensen, Lisa Wissler, Thomas Hansson. Discovery of indazole ethers as novel, potent, non-steroidal glucocorticoid receptor modulators. Bioorganic & Medicinal Chemistry Letters 2016, 26 (23) , 5741-5748. https://doi.org/10.1016/j.bmcl.2016.10.052
    29. Paolo Montuschi, Mario Malerba, Giuseppe Macis, Nadia Mores, Giuseppe Santini. Triple inhaled therapy for chronic obstructive pulmonary disease. Drug Discovery Today 2016, 21 (11) , 1820-1827. https://doi.org/10.1016/j.drudis.2016.07.009
    30. Vicky Chang, Emma L. Gray, Paul S. Thomas. Phamacology of fluticasone furoate and vilanterol trifenatate combination therapy for asthma. Expert Review of Respiratory Medicine 2016, 10 (10) , 1069-1078. https://doi.org/10.1080/17476348.2016.1227245
    31. Maurizio Franzini. Corticosteroid Carboxylic Acid Esters. 2016, 245-267. https://doi.org/10.1002/9783527693931.ch18
    32. Ya-Lin Liu, Soonmin Jang, Shih-Min Wang, Chiu-Hao Chen, Feng-Yin Li. Investigation on critical structural motifs of ligands for triggering glucocorticoid receptor nuclear migration through molecular docking simulations. Journal of Biomolecular Structure and Dynamics 2016, 34 (6) , 1214-1231. https://doi.org/10.1080/07391102.2015.1074113
    33. Gustavo J. Rodrigo, Vicente Plaza. Once-daily fluticasone furoate and vilanterol for adolescents and adults with symptomatic asthma. Annals of Allergy, Asthma & Immunology 2016, 116 (6) , 565-570. https://doi.org/10.1016/j.anai.2016.03.035
    34. Hiroshi Chantaphakul, Kiat Ruxrungtham. Fixed-Dose combination of the inhaled corticosteroid and long-acting beta 2 -agonist therapy in adults with persistent asthma. Expert Opinion on Pharmacotherapy 2016, 17 (5) , 631-642. https://doi.org/10.1517/14656566.2016.1145659
    35. R.D. Kempsford, J. Bal, A. Baines, J. Renaux, R. Ravindranath, P.S. Thomas. The efficacy of fluticasone furoate administered in the morning or evening is comparable in patients with persistent asthma. Respiratory Medicine 2016, 112 , 18-24. https://doi.org/10.1016/j.rmed.2015.12.011
    36. Yuanzheng He, Jingjing Shi, Wei Yi, Xin Ren, Xiang Gao, Jianshuang Li, Nanyan Wu, Kevin Weaver, Qian Xie, Sok Kean Khoo, Tao Yang, Xiaozhu Huang, Karsten Melcher, H Eric Xu. Discovery of a highly potent glucocorticoid for asthma treatment. Cell Discovery 2015, 1 (1) https://doi.org/10.1038/celldisc.2015.35
    37. E V Nazarova, E A Latysheva. Relvar Ellipta® - new molecule in a new delivery system - new horizons in the treatment of bronchial asthma. Russian Journal of Allergy 2015, 12 (5) , 82-89. https://doi.org/10.36691/RJA457
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    39. Yahiya Y. Syed. Fluticasone Furoate/Vilanterol: a Review of Its Use in Patients with Asthma. Drugs 2015, 75 (4) , 407-418. https://doi.org/10.1007/s40265-015-0354-5
    40. Guillaume A. Schoch, Massimo Sammito, Claudia Millán, Isabel Usón, Markus G. Rudolph. Structure of a 13-fold superhelix (almost) determined from first principles. IUCrJ 2015, 2 (2) , 177-187. https://doi.org/10.1107/S2052252515000238
    41. T Joshi, M Johnson, R Newton, M Giembycz. An analysis of glucocorticoid receptor-mediated gene expression in BEAS-2B human airway epithelial cells identifies distinct, ligand-directed, transcription profiles with implications for asthma therapeutics. British Journal of Pharmacology 2015, 172 (5) , 1360-1378. https://doi.org/10.1111/bph.13014
    42. V. Prakash Reddy. Organofluorine Pharmaceuticals. 2015, 133-178. https://doi.org/10.1016/B978-0-444-53748-5.00005-8
    43. Steven Swallow. Fluorine in Medicinal Chemistry. 2015, 65-133. https://doi.org/10.1016/bs.pmch.2014.11.001
    44. Ashley Woodcock, Jan Lötvall, William W Busse, Eric D Bateman, Sally Stone, Anna Ellsworth, Loretta Jacques. Efficacy and safety of fluticasone furoate 100 μg and 200 μg once daily in the treatment of moderate-severe asthma in adults and adolescents: a 24-week randomised study. BMC Pulmonary Medicine 2014, 14 (1) https://doi.org/10.1186/1471-2466-14-113
    45. W. W. Busse, E. D. Bateman, P. M. O'Byrne, J. Lötvall, A. Woodcock, H. Medley, R. Forth, L. Jacques. Once‐daily fluticasone furoate 50 mcg in mild‐to‐moderate asthma: a 24‐week placebo‐controlled randomized trial. Allergy 2014, 69 (11) , 1522-1530. https://doi.org/10.1111/all.12480
    46. Kate McKeage. Fluticasone Furoate/Vilanterol: A Review of Its Use in Chronic Obstructive Pulmonary Disease. Drugs 2014, 74 (13) , 1509-1522. https://doi.org/10.1007/s40265-014-0269-6
    47. Eugene R. Bleecker, Jan Lötvall, Paul M. O'Byrne, Ashley Woodcock, William W. Busse, Edward M. Kerwin, Richard Forth, Hilary V. Medley, Carol Nunn, Loretta Jacques, Eric D. Bateman. Fluticasone Furoate–Vilanterol 100-25 mcg Compared with Fluticasone Furoate 100 mcg in Asthma: A Randomized Trial. The Journal of Allergy and Clinical Immunology: In Practice 2014, 2 (5) , 553-561. https://doi.org/10.1016/j.jaip.2014.02.010
    48. Mark T. Dransfield, Gregory Feldman, Phillip Korenblat, Craig F. LaForce, Nicholas Locantore, Massimo Pistolesi, Michael L. Watkins, Courtney Crim, Fernando J. Martinez. Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients. Respiratory Medicine 2014, 108 (8) , 1171-1179. https://doi.org/10.1016/j.rmed.2014.05.008
    49. Karl Edman, Ragnhild Ahlgren, Malena Bengtsson, Håkan Bladh, Stefan Bäckström, Jan Dahmén, Krister Henriksson, Per Hillertz, Vijakumar Hulikal, Anders Jerre, Liz Kinchin, Charlotte Kåse, Matti Lepistö, Irene Mile, Stinabritt Nilsson, Amir Smailagic, John Taylor, Ann Tjörnebo, Lisa Wissler, Thomas Hansson. The discovery of potent and selective non-steroidal glucocorticoid receptor modulators, suitable for inhalation. Bioorganic & Medicinal Chemistry Letters 2014, 24 (11) , 2571-2577. https://doi.org/10.1016/j.bmcl.2014.03.070
    50. Yuanzheng He, Wei Yi, Kelly Suino-Powell, X Edward Zhou, W David Tolbert, Xiaobo Tang, Jing Yang, Huaiyu Yang, Jingjing Shi, Li Hou, Hualiang Jiang, Karsten Melcher, H Eric Xu. Structures and mechanism for the design of highly potent glucocorticoids. Cell Research 2014, 24 (6) , 713-726. https://doi.org/10.1038/cr.2014.52
    51. Eric D Bateman, Paul M O'Byrne, William W Busse, Jan Lötvall, Eugene R Bleecker, Leslie Andersen, Loretta Jacques, Lucy Frith, Jessica Lim, Ashley Woodcock. Once-daily fluticasone furoate (FF)/vilanterol reduces risk of severe exacerbations in asthma versus FF alone. Thorax 2014, 69 (4) , 312-319. https://doi.org/10.1136/thoraxjnl-2013-203600
    52. Jan Lötvall, Eugene R. Bleecker, William W. Busse, Paul M. O'Byrne, Ashley Woodcock, Edward M. Kerwin, Sally Stone, Richard Forth, Loretta Jacques, Eric D. Bateman. Efficacy and safety of fluticasone furoate 100 μg once-daily in patients with persistent asthma: A 24-week placebo and active-controlled randomised trial. Respiratory Medicine 2014, 108 (1) , 41-49. https://doi.org/10.1016/j.rmed.2013.11.009
    53. Fraydoon Rastinejad, Pengxiang Huang, Vikas Chandra, Sepideh Khorasanizadeh. Understanding nuclear receptor form and function using structural biology. Journal of Molecular Endocrinology 2013, 51 (3) , T1-T21. https://doi.org/10.1530/JME-13-0173
    54. Ann Allen, Isabelle Schenkenberger, Roopa Trivedi, Jeremy Cole, Wesley Hicks, Nadeem Gul, Loretta Jacques. Inhaled fluticasone furoate/vilanterol does not affect hypothalamic‐pituitary‐adrenal axis function in adolescent and adult asthma: randomised, double‐blind, placebo‐controlled study. The Clinical Respiratory Journal 2013, 7 (4) , 397-406. https://doi.org/10.1111/crj.12026
    55. Peter Norman. Crystalline forms of 2,2,2-trifluoro- N -[(1 R ,2 S )-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3-methoxyphenyl)-2-propanyl]acetamide (AZD-5423). Expert Opinion on Therapeutic Patents 2013, 23 (9) , 1239-1245. https://doi.org/10.1517/13543776.2013.820706
    56. I J Uings, D Needham, J Matthews, M Haase, R Austin, D Angell, K Leavens, J Holt, K Biggadike, S N Farrow. Discovery of GW870086: a potent anti-inflammatory steroid with a unique pharmacological profile. British Journal of Pharmacology 2013, 169 (6) , 1389-1403. https://doi.org/10.1111/bph.12232
    57. Eugene R. Bleecker, Eric D. Bateman, William W. Busse, Ashley Woodcock, Lucy Frith, Karen W. House, Loretta Jacques, Angela M. Davis, Brett Haumann, Jan Lötvall. Once-daily fluticasone furoate is efficacious in patients with symptomatic asthma on low-dose inhaled corticosteroids. Annals of Allergy, Asthma & Immunology 2012, 109 (5) , 353-358.e4. https://doi.org/10.1016/j.anai.2012.08.017
    58. Sumitra Sengupta, William H. Bisson, Lijoy K. Mathew, Siva K. Kolluri, Robert L. Tanguay. Alternate glucocorticoid receptor ligand binding structures influence outcomes in an in vivo tissue regeneration model. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2012, 156 (2) , 121-129. https://doi.org/10.1016/j.cbpc.2012.05.003
    59. HOSSEIN RAZAVI, CHRISTIAN HARCKEN. Non-steroidal Dissociated Glucocorticoid Receptor Agonists. 2012, 481-516. https://doi.org/10.1039/9781849735346-00481
    60. Jeffrey A. Kohn, Kirti Deshpande, Eric A. Ortlund. Deciphering Modern Glucocorticoid Cross-pharmacology Using Ancestral Corticosteroid Receptors. Journal of Biological Chemistry 2012, 287 (20) , 16267-16275. https://doi.org/10.1074/jbc.M112.346411
    61. Eric D. Bateman, Eugene R. Bleecker, Jan Lötvall, Ashley Woodcock, Richard Forth, Hilary Medley, Angela M. Davis, Loretta Jacques, Brett Haumann, William W. Busse. Dose effect of once-daily fluticasone furoate in persistent asthma: A randomized trial. Respiratory Medicine 2012, 106 (5) , 642-650. https://doi.org/10.1016/j.rmed.2012.01.004
    62. Ashley Woodcock, Eric D Bateman, William W Busse, Jan Lötvall, Neil G Snowise, Richard Forth, Loretta Jacques, Brett Haumann, Eugene R Bleecker. Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial. Respiratory Research 2011, 12 (1) https://doi.org/10.1186/1465-9921-12-132
    63. Ashley Woodcock, Eugene R Bleecker, William W Busse, Jan Lötvall, Neil G Snowise, Lucy Frith, Loretta Jacques, Brett Haumann, Eric D Bateman. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma. Respiratory Research 2011, 12 (1) https://doi.org/10.1186/1465-9921-12-160
    64. Christos Rossios, Yasuo To, Masako To, Misako Ito, Peter J. Barnes, Ian M. Adcock, Malcolm Johnson, Kazuhiro Ito. Long-acting fluticasone furoate has a superior pharmacological profile to fluticasone propionate in human respiratory cells. European Journal of Pharmacology 2011, 670 (1) , 244-251. https://doi.org/10.1016/j.ejphar.2011.08.022
    65. Elisa Villa, Maria Sandra Magnoni, Dino Micheli, Giorgio Walter Canonica. A review of the use of fluticasone furoate since its launch. Expert Opinion on Pharmacotherapy 2011, 12 (13) , 2107-2117. https://doi.org/10.1517/14656566.2011.600688
    66. Keith Biggadike. Fluticasone furoate/fluticasone propionate - different drugs with different properties. The Clinical Respiratory Journal 2011, 5 (3) , 183-184. https://doi.org/10.1111/j.1752-699X.2011.00244.x
    67. Peter Norman. Boehringer Ingleheim's selective glucocorticoid receptor agonist development candidate: evaluation of WO2010141331, WO2010141332 and WO2010141333. Expert Opinion on Therapeutic Patents 2011, 21 (7) , 1137-1142. https://doi.org/10.1517/13543776.2011.581229
    68. O M Kurbacheva, K S Pavlova. SAFETY OF INTRANASAL CORTICOSTEROIDS. Russian Journal of Allergy 2010, 7 (6) , 64-68. https://doi.org/10.36691/RJA933
    69. Tobias Seitz, Ralf Thoma, Guillaume A. Schoch, Martine Stihle, Jörg Benz, Brigitte D'Arcy, Andrea Wiget, Armin Ruf, Michael Hennig, Reinhard Sterner. Enhancing the Stability and Solubility of the Glucocorticoid Receptor Ligand-Binding Domain by High-Throughput Library Screening. Journal of Molecular Biology 2010, 403 (4) , 562-577. https://doi.org/10.1016/j.jmb.2010.08.048
    70. Diego M. Presman, Lautaro D. Alvarez, Valeria Levi, Silvina Eduardo, Michelle A. Digman, Marcelo A. Martí, Adriana S. Veleiro, Gerardo Burton, Adali Pecci, . Insights on Glucocorticoid Receptor Activity Modulation through the Binding of Rigid Steroids. PLoS ONE 2010, 5 (10) , e13279. https://doi.org/10.1371/journal.pone.0013279
    71. Per-Ola Önnervik, Maria Lindahl, Naila Svitacheva, Martin Stämpfli, Kerstin Thim, Amir Smailagic, Robert Virtala, John D. Taylor. The role of the CCR1 receptor in the inflammatory response to tobacco smoke in a mouse model. Inflammation Research 2010, 59 (10) , 817-825. https://doi.org/10.1007/s00011-010-0193-5
    72. Mitchell A. Avery, Amar G. Chittiboyina. Anti‐Inflammatory Glucocorticoids. 2010, 35-152. https://doi.org/10.1002/0471266949.bmc192
    73. Adriana S. Veleiro, Lautaro D. Alvarez, Silvina L. Eduardo, Gerardo Burton. Structure of the Glucocorticoid Receptor, a Flexible Protein That Can Adapt to Different Ligands. ChemMedChem 2010, 5 (5) , 649-659. https://doi.org/10.1002/cmdc.201000014
    74. Samuel J. Pfaff, Robert J. Fletterick. Hormone Binding and Co-regulator Binding to the Glucocorticoid Receptor are Allosterically Coupled. Journal of Biological Chemistry 2010, 285 (20) , 15256-15267. https://doi.org/10.1074/jbc.M110.108118
    75. Pengxiang Huang, Vikas Chandra, Fraydoon Rastinejad. Structural Overview of the Nuclear Receptor Superfamily: Insights into Physiology and Therapeutics. Annual Review of Physiology 2010, 72 (1) , 247-272. https://doi.org/10.1146/annurev-physiol-021909-135917
    76. Guillaume A. Schoch, Brigitte D'Arcy, Martine Stihle, Dominique Burger, Dominik Bär, Jörg Benz, Ralf Thoma, Armin Ruf. Molecular Switch in the Glucocorticoid Receptor: Active and Passive Antagonist Conformations. Journal of Molecular Biology 2010, 395 (3) , 568-577. https://doi.org/10.1016/j.jmb.2009.11.011
    77. Ben Bardsley, Marco S. Smith, Bob H. Gibbon. Structure elucidation and spectroscopic analysis of photodegradants of the anti-rhinitis drug fluticasone furoate. Organic & Biomolecular Chemistry 2010, 8 (8) , 1876. https://doi.org/10.1039/b926964a
    78. James R. Hanson. Steroids: partial synthesis in medicinal chemistry. Natural Product Reports 2010, 27 (6) , 887. https://doi.org/10.1039/c001262a
    79. Keith Biggadike, Randy K. Bledsoe, Diane M. Coe, Tony W. J. Cooper, David House, Marie A. Iannone, Simon J. F. Macdonald, Kevin P. Madauss, Iain M. McLay, Tracy J. Shipley, Simon J. Taylor, Thuy B. Tran, Iain J. Uings, Victoria Weller, Shawn P. Williams. Design and x-ray crystal structures of high-potency nonsteroidal glucocorticoid agonists exploiting a novel binding site on the receptor. Proceedings of the National Academy of Sciences 2009, 106 (43) , 18114-18119. https://doi.org/10.1073/pnas.0909125106
    80. Valeria Onnis, Gemma K Kinsella, Giorgio Carta, Darren Fayne, David G Lloyd. Rational ligand-based virtual screening and structure–activity relationship studies in the ligand-binding domain of the glucocorticoid receptor-α. Future Medicinal Chemistry 2009, 1 (3) , 483-499. https://doi.org/10.4155/fmc.09.39
    81. Valeria Onnis, Gemma K Kinsella, Giorgio Carta, Darren Fayne, David G Lloyd. Rational structure-based drug design and optimization in the ligand-binding domain of the glucocorticoid receptor-α. Future Medicinal Chemistry 2009, 1 (2) , 345-359. https://doi.org/10.4155/fmc.09.21
    82. Heather A. Barnett, Diane M. Coe, Tony W.J. Cooper, Torquil I. Jack, Haydn T. Jones, Simon J.F. Macdonald, Iain M. McLay, Natalie Rayner, Rosemary Z. Sasse, Tracy J. Shipley, Phil A. Skone, Graham I. Somers, Simon Taylor, Iain J. Uings, James M. Woolven, Gordon G. Weingarten. Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists. Bioorganic & Medicinal Chemistry Letters 2009, 19 (1) , 158-162. https://doi.org/10.1016/j.bmcl.2008.10.128
    83. Yong Xu, Tao Zhang, Minbo Chen. Combining 3D-QSAR, docking, molecular dynamics and MM/PBSA methods to predict binding modes for nonsteroidal selective modulator to glucocorticoid receptor. Bioorganic & Medicinal Chemistry Letters 2009, 19 (2) , 393-396. https://doi.org/10.1016/j.bmcl.2008.11.069
    84. Kevin P. Madauss, Randy K. Bledsoe, Iain Mclay, Eugene L. Stewart, Iain J. Uings, Gordon Weingarten, Shawn P. Williams. The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist. Bioorganic & Medicinal Chemistry Letters 2008, 18 (23) , 6097-6099. https://doi.org/10.1016/j.bmcl.2008.10.021

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