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A surface on the androgen receptor that allosterically regulates coactivator binding.

Estébanez-Perpiñá E, Arnold LA, Arnold AA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ
Proc Natl Acad Sci U S A 104 16074-9 (2007)
Related entries: 2pio, 2pip, 2piq, 2pir, 2pit, 2piu, 2piv, 2pix, 2pkl, 2qpy

Cited: 165 times
EuropePMC logo PMID: 17911242

Abstract

Current approaches to inhibit nuclear receptor (NR) activity target the hormone binding pocket but face limitations. We have proposed that inhibitors, which bind to nuclear receptor surfaces that mediate assembly of the receptor's binding partners, might overcome some of these limitations. The androgen receptor (AR) plays a central role in prostate cancer, but conventional inhibitors lose effectiveness as cancer treatments because anti-androgen resistance usually develops. We conducted functional and x-ray screens to identify compounds that bind the AR surface and block binding of coactivators for AR activation function 2 (AF-2). Four compounds that block coactivator binding in solution with IC(50) approximately 50 microM and inhibit AF-2 activity in cells were detected: three nonsteroidal antiinflammatory drugs and the thyroid hormone 3,3',5-triiodothyroacetic acid. Although visualization of compounds at the AR surface reveals weak binding at AF-2, the most potent inhibitors bind preferentially to a previously unknown regulatory surface cleft termed binding function (BF)-3, which is a known target for mutations in prostate cancer and androgen insensitivity syndrome. X-ray structural analysis reveals that 3,3',5-triiodothyroacetic acid binding to BF-3 remodels the adjacent interaction site AF-2 to weaken coactivator binding. Mutation of residues that form BF-3 inhibits AR function and AR AF-2 activity. We propose that BF-3 is a previously unrecognized allosteric regulatory site needed for AR activity in vivo and a possible pharmaceutical target.

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  1. Structural insight into effector proteins of Gram-negative bacterial pathogens that modulate the phosphoproteome of their host. Grishin AM, Beyrakhova KA, Cygler M. Protein Sci 24 604-620 (2015)
  2. Androgen Receptor in Hormone Receptor-Positive Breast Cancer. Khan AF, Karami S, Peidl AS, Waiters KD, Babajide MF, Bawa-Khalfe T. Int J Mol Sci 25 476 (2023)

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  1. A surface on the androgen receptor that allosterically regulates coactivator binding. Estébanez-Perpiñá E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ. Proc Natl Acad Sci U S A 104 16074-16079 (2007)
  2. Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets. Chen Z, Li HL, Zhang QJ, Bao XG, Yu KQ, Luo XM, Zhu WL, Jiang HL. Acta Pharmacol Sin 30 1694-1708 (2009)
  3. Coregulator control of androgen receptor action by a novel nuclear receptor-binding motif. Jehle K, Cato L, Neeb A, Muhle-Goll C, Jung N, Smith EW, Buzon V, Carbó LR, Estébanez-Perpiñá E, Schmitz K, Fruk L, Luy B, Chen Y, Cox MB, Bräse S, Brown M, Cato AC. J Biol Chem 289 8839-8851 (2014)
  4. Cosolvent Analysis Toolkit (CAT): a robust hotspot identification platform for cosolvent simulations of proteins to expand the druggable proteome. Sabanés Zariquiey F, de Souza JV, Bronowska AK. Sci Rep 9 19118 (2019)
  5. Therapeutic Potential of Leelamine, a Novel Inhibitor of Androgen Receptor and Castration-Resistant Prostate Cancer. Singh KB, Ji X, Singh SV. Mol Cancer Ther 17 2079-2090 (2018)
  6. Virtual screening of potentially endocrine-disrupting chemicals against nuclear receptors and its application to identify PPARγ-bound fatty acids. Jaladanki CK, He Y, Zhao LN, Maurer-Stroh S, Loo LH, Song H, Fan H. Arch Toxicol 95 355-374 (2021)
  7. Hits Discovery on the Androgen Receptor: In Silico Approaches to Identify Agonist Compounds. Réau M, Lagarde N, Zagury JF, Montes M. Cells 8 E1431 (2019)
  8. An Assay on the Possible Effect of Essential Oil Constituents on Receptors Involved in Women's Hormonal Health and Reproductive System Diseases. Sakhteman A, Pasdaran A, Afifi M, Hamedi A. J Evid Based Integr Med 25 2515690X20932527 (2020)
  9. Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide. Zhang K, Zhang C, Teng X, Wang K, Chen M. Sci Rep 13 5417 (2023)
  10. Computational biology and in vitro studies for anticipating cancer-related molecular targets of sweet wormwood (Artemisia annua). Dawood H, Celik I, Ibrahim RS. BMC Complement Med Ther 23 312 (2023)
  11. Identification of Constituents and Exploring the Mechanism for Toutongning Capsule in the Treatment of Migraine. Du X, Di Z, Liu Y, Zhi W, Liu Y, Zhang H, Liu F. Evid Based Complement Alternat Med 2022 5528845 (2022)
  12. Indocyanine Green-based Glow Nanoparticles Probe for Cancer Imaging. Chauhan N, Cabrera M, Chowdhury P, Nagesh PKB, Dhasmana A, Pranav, Jaggi M, Chauhan SC, Yallapu MM. Nanotheranostics 7 353-367 (2023)


Reviews citing this publication (55)

  1. Androgen receptor: structure, role in prostate cancer and drug discovery. Tan MH, Li J, Xu HE, Melcher K, Yong EL. Acta Pharmacol Sin 36 3-23 (2015)
  2. Androgen insensitivity syndrome. Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J. Lancet 380 1419-1428 (2012)
  3. Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Claessens F, Denayer S, Van Tilborgh N, Kerkhofs S, Helsen C, Haelens A. Nucl Recept Signal 6 e008 (2008)
  4. Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation. Changeux JP, Christopoulos A. Cell 166 1084-1102 (2016)
  5. Small molecule inhibitors targeting the "achilles' heel" of androgen receptor activity. Sadar MD. Cancer Res 71 1208-1213 (2011)
  6. AKR1C3 as a target in castrate resistant prostate cancer. Adeniji AO, Chen M, Penning TM. J Steroid Biochem Mol Biol 137 136-149 (2013)
  7. Anticancer steroids: linking natural and semi-synthetic compounds. Salvador JA, Carvalho JF, Neves MA, Silvestre SM, Leitão AJ, Silva MM, Sá e Melo ML. Nat Prod Rep 30 324-374 (2013)
  8. Allosteric modulators of steroid hormone receptors: structural dynamics and gene regulation. Kumar R, McEwan IJ. Endocr Rev 33 271-299 (2012)
  9. Androgen insensitivity syndrome. Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Best Pract Res Clin Endocrinol Metab 29 569-580 (2015)
  10. Androgen receptor antagonists for prostate cancer therapy. Helsen C, Van den Broeck T, Voet A, Prekovic S, Van Poppel H, Joniau S, Claessens F. Endocr Relat Cancer 21 T105-18 (2014)
  11. Minireview: dynamic structures of nuclear hormone receptors: new promises and challenges. Simons SS, Edwards DP, Kumar R. Mol Endocrinol 28 173-182 (2014)
  12. A conserved surface on the ligand binding domain of nuclear receptors for allosteric control. Buzón V, Carbó LR, Estruch SB, Fletterick RJ, Estébanez-Perpiñá E. Mol Cell Endocrinol 348 394-402 (2012)
  13. Intrinsic disorder in the androgen receptor: identification, characterisation and drugability. McEwan IJ. Mol Biosyst 8 82-90 (2012)
  14. Regulation of steroid hormone receptor function by the 52-kDa FK506-binding protein (FKBP52). Sivils JC, Storer CL, Galigniana MD, Cox MB. Curr Opin Pharmacol 11 314-319 (2011)
  15. Beyond the ligand-binding pocket: targeting alternate sites in nuclear receptors. Caboni L, Lloyd DG. Med Res Rev 33 1081-1118 (2013)
  16. Constitutive activity of the androgen receptor. Chan SC, Dehm SM. Adv Pharmacol 70 327-366 (2014)
  17. Allosteric controls of nuclear receptor function in the regulation of transcription. Billas I, Moras D. J Mol Biol 425 2317-2329 (2013)
  18. Recent developments in antiandrogens and selective androgen receptor modulators. Haendler B, Cleve A. Mol Cell Endocrinol 352 79-91 (2012)
  19. Transcriptional switches: chemical approaches to gene regulation. Lee LW, Mapp AK. J Biol Chem 285 11033-11038 (2010)
  20. Targeting alternative sites on the androgen receptor to treat castration-resistant prostate cancer. Lallous N, Dalal K, Cherkasov A, Rennie PS. Int J Mol Sci 14 12496-12519 (2013)
  21. Role of the androgen receptor CAG repeat polymorphism in prostate cancer, and spinal and bulbar muscular atrophy. Kumar R, Atamna H, Zakharov MN, Bhasin S, Khan SH, Jasuja R. Life Sci 88 565-571 (2011)
  22. Eighty Years of Targeting Androgen Receptor Activity in Prostate Cancer: The Fight Goes on. Estébanez-Perpiñá E, Bevan CL, McEwan IJ. Cancers (Basel) 13 509 (2021)
  23. Small molecule inhibitors as probes for estrogen and androgen receptor action. Shapiro DJ, Mao C, Cherian MT. J Biol Chem 286 4043-4048 (2011)
  24. Allosteric modulation as a unifying mechanism for receptor function and regulation. Changeux JP, Christopoulos A. Diabetes Obes Metab 19 Suppl 1 4-21 (2017)
  25. Steroid Receptor-Associated Immunophilins: A Gateway to Steroid Signalling. Ratajczak T, Cluning C, Ward BK. Clin Biochem Rev 36 31-52 (2015)
  26. Androgen receptor gene rearrangements: new perspectives on prostate cancer progression. Brand LJ, Dehm SM. Curr Drug Targets 14 441-449 (2013)
  27. Calmodulin, a regulatory partner of the estrogen receptor alpha in breast cancer cells. Gallo D, Jacquot Y, Laurent G, Leclercq G. Mol Cell Endocrinol 291 20-26 (2008)
  28. Glucocorticoid receptor cofactors as therapeutic targets. Simons SS. Curr Opin Pharmacol 10 613-619 (2010)
  29. Androgen insensitivity syndrome. Tadokoro-Cuccaro R, Hughes IA. Curr Opin Endocrinol Diabetes Obes 21 499-503 (2014)
  30. Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer. Chai SC, Wright WC, Chen T. Med Res Rev 40 1061-1083 (2020)
  31. The road less traveled: new views of steroid receptor action from the path of dose-response curves. Simons SS, Chow CC. Mol Cell Endocrinol 348 373-382 (2012)
  32. On the specificity of protein-protein interactions in the context of disorder. Teilum K, Olsen JG, Kragelund BB. Biochem J 478 2035-2050 (2021)
  33. Advances in small molecule inhibitors of androgen receptor for the treatment of advanced prostate cancer. Sadar MD. World J Urol 30 311-318 (2012)
  34. Computer-Aided Ligand Discovery for Estrogen Receptor Alpha. Bafna D, Ban F, Rennie PS, Singh K, Cherkasov A. Int J Mol Sci 21 E4193 (2020)
  35. Botanical compounds and their regulation of nuclear receptor action: the case of traditional Chinese medicine. Li L, Bonneton F, Chen XY, Laudet V. Mol Cell Endocrinol 401 221-237 (2015)
  36. Structures of androgen receptor bound with ligands: advancing understanding of biological functions and drug discovery. Sakkiah S, Ng HW, Tong W, Hong H. Expert Opin Ther Targets 20 1267-1282 (2016)
  37. Targeting the androgen receptor with steroid conjugates. Levine PM, Garabedian MJ, Kirshenbaum K. J Med Chem 57 8224-8237 (2014)
  38. Allosteric pathways in nuclear receptors - Potential targets for drug design. Fernandez EJ. Pharmacol Ther 183 152-159 (2018)
  39. Biological relevance of Hsp90-binding immunophilins in cancer development and treatment. Mazaira GI, Camisay MF, De Leo S, Erlejman AG, Galigniana MD. Int J Cancer 138 797-808 (2016)
  40. Steroid receptor/coactivator binding inhibitors: An update. Skowron KJ, Booker K, Cheng C, Creed S, David BP, Lazzara PR, Lian A, Siddiqui Z, Speltz TE, Moore TW. Mol Cell Endocrinol 493 110471 (2019)
  41. Allosteric mechanisms of nuclear receptors: insights from computational simulations. Mackinnon JA, Gallastegui N, Osguthorpe DJ, Hagler AT, Estébanez-Perpiñá E. Mol Cell Endocrinol 393 75-82 (2014)
  42. Androgen Receptor Dependence. Chaturvedi AP, Dehm SM. Adv Exp Med Biol 1210 333-350 (2019)
  43. Endocrine Disrupting Chemicals Mediated through Binding Androgen Receptor Are Associated with Diabetes Mellitus. Sakkiah S, Wang T, Zou W, Wang Y, Pan B, Tong W, Hong H. Int J Environ Res Public Health 15 E25 (2017)
  44. Alternative binding sites at the vitamin D receptor and their ligands. Mutchie TR, Yu OB, Di Milo ES, Arnold LA. Mol Cell Endocrinol 485 1-8 (2019)
  45. Developments in nonsteroidal antiandrogens targeting the androgen receptor. Liu B, Su L, Geng J, Liu J, Zhao G. ChemMedChem 5 1651-1661 (2010)
  46. Allosteric Modulation of Adenosine A2A Receptors as a New Therapeutic Avenue. Korkutata M, Agrawal L, Lazarus M. Int J Mol Sci 23 2101 (2022)
  47. Androgen receptor modulators: a marriage of chemistry and biology. McEwan IJ. Future Med Chem 5 1109-1120 (2013)
  48. Structural aspects of thyroid hormone binding to proteins and competitive interactions with natural and synthetic compounds. Schweizer U, Towell H, Vit A, Rodriguez-Ruiz A, Steegborn C. Mol Cell Endocrinol 458 57-67 (2017)
  49. Competitive Agonists and Antagonists of Steroid Nuclear Receptors: Evolution of the Concept or Its Reversal. Smirnova OV. Biochemistry (Mosc) 80 1227-1234 (2015)
  50. Cheminformatics Driven Development of Novel Therapies for Drug Resistant Prostate Cancer. Ban F, Dalal K, LeBlanc E, Morin H, Rennie PS, Cherkasov A. Mol Inform 37 e1800043 (2018)
  51. Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer. Martinez-Ariza G, Hulme C. Pharm Pat Anal 4 387-402 (2015)
  52. The role of ubiquitination in spinal and bulbar muscular atrophy. Sengupta M, Pluciennik A, Merry DE. Front Mol Neurosci 15 1020143 (2022)
  53. Allosteric Antagonism of the Pregnane X Receptor (PXR): Current-State-of-the-Art and Prediction of Novel Allosteric Sites. Kamaraj R, Drastik M, Maixnerova J, Pavek P. Cells 11 2974 (2022)
  54. Recent applications of computational methods to allosteric drug discovery. Govindaraj RG, Thangapandian S, Schauperl M, Denny RA, Diller DJ. Front Mol Biosci 9 1070328 (2022)
  55. The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease. Meszaros A, Ahmed J, Russo G, Tompa P, Lazar T. Front Med (Lausanne) 9 1019803 (2022)

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  1. Nonbonding interactions of organic halogens in biological systems: implications for drug discovery and biomolecular design. Lu Y, Wang Y, Zhu W. Phys Chem Chem Phys 12 4543-4551 (2010)
  2. Drug Repurposing from an Academic Perspective. Oprea TI, Bauman JE, Bologa CG, Buranda T, Chigaev A, Edwards BS, Jarvik JW, Gresham HD, Haynes MK, Hjelle B, Hromas R, Hudson L, Mackenzie DA, Muller CY, Reed JC, Simons PC, Smagley Y, Strouse J, Surviladze Z, Thompson T, Ursu O, Waller A, Wandinger-Ness A, Winter SS, Wu Y, Young SM, Larson RS, Willman C, Sklar LA. Drug Discov Today Ther Strateg 8 61-69 (2011)
  3. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A. Genome Biol 17 10 (2016)
  4. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands. Christopoulos A, Changeux JP, Catterall WA, Fabbro D, Burris TP, Cidlowski JA, Olsen RW, Peters JA, Neubig RR, Pin JP, Sexton PM, Kenakin TP, Ehlert FJ, Spedding M, Langmead CJ. Pharmacol Rev 66 918-947 (2014)
  5. An alternate binding site for PPARγ ligands. Hughes TS, Giri PK, de Vera IM, Marciano DP, Kuruvilla DS, Shin Y, Blayo AL, Kamenecka TM, Burris TP, Griffin PR, Kojetin DJ. Nat Commun 5 3571 (2014)
  6. Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB. Proc Natl Acad Sci U S A 108 11878-11883 (2011)
  7. Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer. Dalal K, Roshan-Moniri M, Sharma A, Li H, Ban F, Hessein M, Hsing M, Singh K, LeBlanc E, Dehm S, Tomlinson Guns ES, Cherkasov A, Rennie PS. J Biol Chem 289 26417-26429 (2014)
  8. Targeting the binding function 3 (BF3) site of the human androgen receptor through virtual screening. Lack NA, Axerio-Cilies P, Tavassoli P, Han FQ, Chan KH, Feau C, LeBlanc E, Guns ET, Guy RK, Rennie PS, Cherkasov A. J Med Chem 54 8563-8573 (2011)
  9. Structure of the homodimeric androgen receptor ligand-binding domain. Nadal M, Prekovic S, Gallastegui N, Helsen C, Abella M, Zielinska K, Gay M, Vilaseca M, Taulès M, Houtsmuller AB, van Royen ME, Claessens F, Fuentes-Prior P, Estébanez-Perpiñá E. Nat Commun 8 14388 (2017)
  10. Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells. Stender JD, Nwachukwu JC, Kastrati I, Kim Y, Strid T, Yakir M, Srinivasan S, Nowak J, Izard T, Rangarajan ES, Carlson KE, Katzenellenbogen JA, Yao XQ, Grant BJ, Leong HS, Lin CY, Frasor J, Nettles KW, Glass CK. Mol Cell 65 1122-1135.e5 (2017)
  11. Computational discovery of novel low micromolar human pregnane X receptor antagonists. Ekins S, Kholodovych V, Ai N, Sinz M, Gal J, Gera L, Welsh WJ, Bachmann K, Mani S. Mol Pharmacol 74 662-672 (2008)
  12. Allosteric targeting of receptor tyrosine kinases. De Smet F, Christopoulos A, Carmeliet P. Nat Biotechnol 32 1113-1120 (2014)
  13. Evidence for DNA-binding domain--ligand-binding domain communications in the androgen receptor. Helsen C, Dubois V, Verfaillie A, Young J, Trekels M, Vancraenenbroeck R, De Maeyer M, Claessens F. Mol Cell Biol 32 3033-3043 (2012)
  14. The Recognition of Identical Ligands by Unrelated Proteins. Barelier S, Sterling T, O'Meara MJ, Shoichet BK. ACS Chem Biol 10 2772-2784 (2015)
  15. A new small molecule inhibitor of estrogen receptor alpha binding to estrogen response elements blocks estrogen-dependent growth of cancer cells. Mao C, Patterson NM, Cherian MT, Aninye IO, Zhang C, Montoya JB, Cheng J, Putt KS, Hergenrother PJ, Wilson EM, Nardulli AM, Nordeen SK, Shapiro DJ. J Biol Chem 283 12819-12830 (2008)
  16. Allosteric conversation in the androgen receptor ligand-binding domain surfaces. Grosdidier S, Carbó LR, Buzón V, Brooke G, Nguyen P, Baxter JD, Bevan C, Webb P, Estébanez-Perpiñá E, Fernández-Recio J. Mol Endocrinol 26 1078-1090 (2012)
  17. Identification and characterization of fragment binding sites for allosteric ligand design using the site identification by ligand competitive saturation hotspots approach (SILCS-Hotspots). MacKerell AD, Jo S, Lakkaraju SK, Lind C, Yu W. Biochim Biophys Acta Gen Subj 1864 129519 (2020)
  18. Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists. Joseph JD, Wittmann BM, Dwyer MA, Cui H, Dye DA, McDonnell DP, Norris JD. Proc Natl Acad Sci U S A 106 12178-12183 (2009)
  19. Ligand-independent and tissue-selective androgen receptor inhibition by pyrvinium. Lim M, Otto-Duessel M, He M, Su L, Nguyen D, Chin E, Alliston T, Jones JO. ACS Chem Biol 9 692-702 (2014)
  20. Exploring Ligand Stability in Protein Crystal Structures Using Binding Pose Metadynamics. Fusani L, Palmer DS, Somers DO, Wall ID. J Chem Inf Model 60 1528-1539 (2020)
  21. Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis. Hsu CL, Liu JS, Wu PL, Guan HH, Chen YL, Lin AC, Ting HJ, Pang ST, Yeh SD, Ma WL, Chen CJ, Wu WG, Chang C. Mol Oncol 8 1575-1587 (2014)
  22. Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy. Badders NM, Korff A, Miranda HC, Vuppala PK, Smith RB, Winborn BJ, Quemin ER, Sopher BL, Dearman J, Messing J, Kim NC, Moore J, Freibaum BD, Kanagaraj AP, Fan B, Tillman H, Chen PC, Wang Y, Freeman BB, Li Y, Kim HJ, La Spada AR, Taylor JP. Nat Med 24 427-437 (2018)
  23. Synthesis of novel ketoconazole derivatives as inhibitors of the human Pregnane X Receptor (PXR; NR1I2; also termed SXR, PAR). Das BC, Madhukumar AV, Anguiano J, Kim S, Sinz M, Zvyaga TA, Power EC, Ganellin CR, Mani S. Bioorg Med Chem Lett 18 3974-3977 (2008)
  24. Direct interdomain interactions can mediate allosterism in the thyroid receptor. Putcha BD, Fernandez EJ. J Biol Chem 284 22517-22524 (2009)
  25. A competitive inhibitor that reduces recruitment of androgen receptor to androgen-responsive genes. Cherian MT, Wilson EM, Shapiro DJ. J Biol Chem 287 23368-23380 (2012)
  26. AR inhibitors identified by high-throughput microscopy detection of conformational change and subcellular localization. Jones JO, An WF, Diamond MI. ACS Chem Biol 4 199-208 (2009)
  27. Helix 11 dynamics is critical for constitutive androstane receptor activity. Wright E, Busby SA, Wisecarver S, Vincent J, Griffin PR, Fernandez EJ. Structure 19 37-44 (2011)
  28. Identification of a new hormone-binding site on the surface of thyroid hormone receptor. Souza PC, Puhl AC, Martínez L, Aparício R, Nascimento AS, Figueira AC, Nguyen P, Webb P, Skaf MS, Polikarpov I. Mol Endocrinol 28 534-545 (2014)
  29. A noncompetitive small molecule inhibitor of estrogen-regulated gene expression and breast cancer cell growth that enhances proteasome-dependent degradation of estrogen receptor {alpha}. Kretzer NM, Cherian MT, Mao C, Aninye IO, Reynolds PD, Schiff R, Hergenrother PJ, Nordeen SK, Wilson EM, Shapiro DJ. J Biol Chem 285 41863-41873 (2010)
  30. Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer. Cato L, Neeb A, Sharp A, Buzón V, Ficarro SB, Yang L, Muhle-Goll C, Kuznik NC, Riisnaes R, Nava Rodrigues D, Armant O, Gourain V, Adelmant G, Ntim EA, Westerling T, Dolling D, Rescigno P, Figueiredo I, Fauser F, Wu J, Rottenberg JT, Shatkina L, Ester C, Luy B, Puchta H, Troppmair J, Jung N, Bräse S, Strähle U, Marto JA, Nienhaus GU, Al-Lazikani B, Salvatella X, de Bono JS, Cato AC, Brown M. Elife 6 e27159 (2017)
  31. The oncoprotein BCL11A binds to orphan nuclear receptor TLX and potentiates its transrepressive function. Estruch SB, Buzón V, Carbó LR, Schorova L, Lüders J, Estébanez-Perpiñá E. PLoS One 7 e37963 (2012)
  32. "True" antiandrogens-selective non-ligand-binding pocket disruptors of androgen receptor-coactivator interactions: novel tools for prostate cancer. Caboni L, Kinsella GK, Blanco F, Fayne D, Jagoe WN, Carr M, Williams DC, Meegan MJ, Lloyd DG. J Med Chem 55 1635-1644 (2012)
  33. Modification of the Orthosteric PPARγ Covalent Antagonist Scaffold Yields an Improved Dual-Site Allosteric Inhibitor. Brust R, Lin H, Fuhrmann J, Asteian A, Kamenecka TM, Kojetin DJ. ACS Chem Biol 12 969-978 (2017)
  34. PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation. Zhang Z, Sun Y, Cho YW, Chow CC, Simons SS. J Biol Chem 288 42-58 (2013)
  35. MixMD Probeview: Robust Binding Site Prediction from Cosolvent Simulations. Graham SE, Leja N, Carlson HA. J Chem Inf Model 58 1426-1433 (2018)
  36. Identification of Cryptic Binding Sites Using MixMD with Standard and Accelerated Molecular Dynamics. Smith RD, Carlson HA. J Chem Inf Model 61 1287-1299 (2021)
  37. Molecular determinants of the recognition of ulipristal acetate by oxo-steroid receptors. Petit-Topin I, Fay M, Resche-Rigon M, Ulmann A, Gainer E, Rafestin-Oblin ME, Fagart J. J Steroid Biochem Mol Biol 144 Pt B 427-435 (2014)
  38. Autophagy-related intrinsically disordered proteins in intra-nuclear compartments. Na I, Meng F, Kurgan L, Uversky VN. Mol Biosyst 12 2798-2817 (2016)
  39. Molecular Dynamics Simulations Revealed the Regulation of Ligands to the Interactions between Androgen Receptor and Its Coactivator. Liu N, Zhou W, Guo Y, Wang J, Fu W, Sun H, Li D, Duan M, Hou T. J Chem Inf Model 58 1652-1661 (2018)
  40. The helix 1-3 loop in the glucocorticoid receptor LBD is a regulatory element for FKBP cochaperones. Cluning C, Ward BK, Rea SL, Arulpragasam A, Fuller PJ, Ratajczak T. Mol Endocrinol 27 1020-1035 (2013)
  41. Binding of bisphenol A, bisphenol AF, and bisphenol S on the androgen receptor: Coregulator recruitment and stimulation of potential interaction sites. Perera L, Li Y, Coons LA, Houtman R, van Beuningen R, Goodwin B, Auerbach SS, Teng CT. Toxicol In Vitro 44 287-302 (2017)
  42. Corepressor effect on androgen receptor activity varies with the length of the CAG encoded polyglutamine repeat and is dependent on receptor/corepressor ratio in prostate cancer cells. Buchanan G, Need EF, Barrett JM, Bianco-Miotto T, Thompson VC, Butler LM, Marshall VR, Tilley WD, Coetzee GA. Mol Cell Endocrinol 342 20-31 (2011)
  43. Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators. Ahmad MF, Huff SE, Pink J, Alam I, Zhang A, Perry K, Harris ME, Misko T, Porwal SK, Oleinick NL, Miyagi M, Viswanathan R, Dealwis CG. J Med Chem 58 9498-9509 (2015)
  44. Minoxidil may suppress androgen receptor-related functions. Hsu CL, Liu JS, Lin AC, Yang CH, Chung WH, Wu WG. Oncotarget 5 2187-2197 (2014)
  45. Novel flufenamic acid analogues as inhibitors of androgen receptor mediated transcription. Féau C, Arnold LA, Kosinski A, Zhu F, Connelly M, Guy RK. ACS Chem Biol 4 834-843 (2009)
  46. Separate regions of glucocorticoid receptor, coactivator TIF2, and comodulator STAMP modify different parameters of glucocorticoid-mediated gene induction. Awasthi S, Simons SS. Mol Cell Endocrinol 355 121-134 (2012)
  47. 27-Hydroxycholesterol Is an Estrogen Receptor β-Selective Negative Allosteric Modifier of 17β-Estradiol Binding. Starkey NJE, Li Y, Drenkhahn-Weinaug SK, Liu J, Lubahn DB. Endocrinology 159 1972-1981 (2018)
  48. Ligand induced interaction of thyroid hormone receptor beta with its coregulators. Valadares NF, Polikarpov I, Garratt RC. J Steroid Biochem Mol Biol 112 205-212 (2008)
  49. Androgen receptor antagonism by divalent ethisterone conjugates in castrate-resistant prostate cancer cells. Levine PM, Lee E, Greenfield A, Bonneau R, Logan SK, Garabedian MJ, Kirshenbaum K. ACS Chem Biol 7 1693-1701 (2012)
  50. Probing the Complex Binding Modes of the PPARγ Partial Agonist 2-Chloro-N-(3-chloro-4-((5-chlorobenzo[d]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide (T2384) to Orthosteric and Allosteric Sites with NMR Spectroscopy. Hughes TS, Shang J, Brust R, de Vera IMS, Fuhrmann J, Ruiz C, Cameron MD, Kamenecka TM, Kojetin DJ. J Med Chem 59 10335-10341 (2016)
  51. Structural Dynamics of Agonist and Antagonist Binding to the Androgen Receptor. Azhagiya Singam ER, Tachachartvanich P, La Merrill MA, Smith MT, Durkin KA. J Phys Chem B 123 7657-7666 (2019)
  52. The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling. Storer Samaniego C, Suh JH, Chattopadhyay A, Olivares K, Guy N, Sivils JC, Dey P, Yumoto F, Fletterick RJ, Strom AM, Gustafsson JÅ, Webb P, Cox MB. PLoS One 10 e0134015 (2015)
  53. A bufadienolide derived androgen receptor antagonist with inhibitory activities against prostate cancer cells. Tian HY, Yuan XF, Jin L, Li J, Luo C, Ye WC, Jiang RW. Chem Biol Interact 207 16-22 (2014)
  54. Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells. Brooke GN, Gamble SC, Hough MA, Begum S, Dart DA, Odontiadis M, Powell SM, Fioretti FM, Bryan RA, Waxman J, Wait R, Bevan CL. Mol Cell Proteomics 14 1201-1216 (2015)
  55. Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer. Liang S, Bian X, Liang D, Sivils JC, Neckers LM, Cox MB, Xie H. Pharm Dev Technol 21 121-126 (2016)
  56. Targeting Binding Function-3 of the Androgen Receptor Blocks Its Co-Chaperone Interactions, Nuclear Translocation, and Activation. Lallous N, Leblanc E, Munuganti RS, Hassona MD, Nakouzi NA, Awrey S, Morin H, Roshan-Moniri M, Singh K, Lawn S, Yamazaki T, Adomat HH, Andre C, Daugaard M, Young RN, Guns ES, Rennie PS, Cherkasov A. Mol Cancer Ther 15 2936-2945 (2016)
  57. A natural-product switch for a dynamic protein interface. Scheepstra M, Nieto L, Hirsch AK, Fuchs S, Leysen S, Lam CV, in het Panhuis L, van Boeckel CA, Wienk H, Boelens R, Ottmann C, Milroy LG, Brunsveld L. Angew Chem Int Ed Engl 53 6443-6448 (2014)
  58. A novel mutation F826L in the human androgen receptor in partial androgen insensitivity syndrome; increased NH2-/COOH-terminal domain interaction and TIF2 co-activation. Wong HY, Hoogerbrugge JW, Pang KL, van Leeuwen M, van Royen ME, Molier M, Berrevoets CA, Dooijes D, Dubbink HJ, van de Wijngaart DJ, Wolffenbuttel KP, Trapman J, Kleijer WJ, Drop SL, Grootegoed JA, Brinkmann AO. Mol Cell Endocrinol 292 69-78 (2008)
  59. Antagonizing the Androgen Receptor with a Biomimetic Acyltransferase. Zhang Y, Mantravadi PK, Jobbagy S, Bao W, Koh JT. ACS Chem Biol 11 2797-2802 (2016)
  60. Molecular basis for dimer formation of TRbeta variant D355R. Jouravel N, Sablin E, Togashi M, Baxter JD, Webb P, Fletterick RJ. Proteins 75 111-117 (2009)
  61. Research resource: modulators of glucocorticoid receptor activity identified by a new high-throughput screening assay. Blackford JA, Brimacombe KR, Dougherty EJ, Pradhan M, Shen M, Li Z, Auld DS, Chow CC, Austin CP, Simons SS. Mol Endocrinol 28 1194-1206 (2014)
  62. Severe forms of partial androgen insensitivity syndrome due to p.L830F novel mutation in androgen receptor gene in a Brazilian family. Petroli RJ, Maciel-Guerra AT, Soardi FC, de Calais FL, Guerra-Junior G, de Mello MP. BMC Res Notes 4 173 (2011)
  63. Similarities and differences between two modes of antagonism of the thyroid hormone receptor. Sadana P, Hwang JY, Attia RR, Arnold LA, Neale G, Guy RK. ACS Chem Biol 6 1096-1106 (2011)
  64. Allosteric Binding Sites On Nuclear Receptors: Focus On Drug Efficacy and Selectivity. Fischer A, Smieško M. Int J Mol Sci 21 E534 (2020)
  65. Computational design, synthesis, and evaluation of miniproteins as androgen receptor coactivator mimics. Vaz B, Möcklinghoff S, Folkertsma S, Lusher S, de Vlieg J, Brunsveld L. Chem Commun (Camb) 5377-5379 (2009)
  66. Conformational dynamics of androgen receptors bound to agonists and antagonists. Gim HJ, Park J, Jung ME, Houk KN. Sci Rep 11 15887 (2021)
  67. Design, synthesis and biological evaluation of novel 5-oxo-2-thioxoimidazolidine derivatives as potent androgen receptor antagonists. Ivachtchenko AV, Ivanenkov YA, Mitkin OD, Vorobiev AA, Kuznetsova IV, Shevkun NA, Koryakova AG, Karapetian RN, Trifelenkov AS, Kravchenko DV, Veselov MS, Chufarova NV. Eur J Med Chem 99 51-66 (2015)
  68. Fragment Screening of RORγt Using Cocktail Crystallography: Identification of Simultaneous Binding of Multiple Fragments. Xue Y, Guo H, Hillertz P. ChemMedChem 11 1881-1885 (2016)
  69. Structural Changes Due to Antagonist Binding in Ligand Binding Pocket of Androgen Receptor Elucidated Through Molecular Dynamics Simulations. Sakkiah S, Kusko R, Pan B, Guo W, Ge W, Tong W, Hong H. Front Pharmacol 9 492 (2018)
  70. Computational Analysis of Crystallization Additives for the Identification of New Allosteric Sites. Fogha J, Diharce J, Obled A, Aci-Sèche S, Bonnet P. ACS Omega 5 2114-2122 (2020)
  71. Discovery of non-LBD inhibitor for androgen receptor by structure-guide design. Ryu BJ, Kim N, Kim JT, Koo TS, Yoo SE, Jeong SH, Kim SH, Kang NS. Bioorg Med Chem Lett 23 3887-3890 (2013)
  72. Dynamic profile analysis to characterize dynamics-driven allosteric sites in enzymes. Taguchi J, Kitao A. Biophys Physicobiol 13 117-126 (2016)
  73. Monte Carlo simulations using PELE to identify a protein-protein inhibitor binding site and pose. Díaz L, Soler D, Tresadern G, Buyck C, Perez-Benito L, Saen-Oon S, Guallar V, Soliva R. RSC Adv 10 7058-7064 (2020)
  74. Quantification of a New Anti-Cancer Molecule MJC13 Using a Rapid, Sensitive, and Reliable Liquid Chromatography-Tandem Mass Spectrometry Method. Liang S, Bian X, Sivils J, Neckers LM, Cox MB, Xie H. Am J Mod Chromatogr 1 1-11 (2014)
  75. The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities. Jiménez-Panizo A, Alegre-Martí A, Tettey TT, Fettweis G, Abella M, Antón R, Johnson TA, Kim S, Schiltz RL, Núñez-Barrios I, Font-Díaz J, Caelles C, Valledor AF, Pérez P, Rojas AM, Fernández-Recio J, Presman DM, Hager GL, Fuentes-Prior P, Estébanez-Perpiñá E. Nucleic Acids Res 50 13063-13082 (2022)
  76. 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. Rocha SM, Fagre AC, Latham AS, Cummings JE, Aboellail TA, Reigan P, Aldaz DA, McDermott CP, Popichak KA, Kading RC, Schountz T, Theise ND, Slayden RA, Tjalkens RB. Front Immunol 13 811430 (2022)
  77. AR cooperates with SMAD4 to maintain skeletal muscle homeostasis. Forouhan M, Lim WF, Zanetti-Domingues LC, Tynan CJ, Roberts TC, Malik B, Manzano R, Speciale AA, Ellerington R, Garcia-Guerra A, Fratta P, Sorarú G, Greensmith L, Pennuto M, Wood MJA, Rinaldi C. Acta Neuropathol 143 713-731 (2022)
  78. Characterizing protein domain associations by Small-molecule ligand binding. Li Q, Cheng T, Wang Y, Bryant SH. J Proteome Sci Comput Biol 1 6 (2012)
  79. A novel chemo-phenotypic method identifies mixtures of salpn, vitamin D3, and pesticides involved in the development of colorectal and pancreatic cancer. Issa NT, Wathieu H, Glasgow E, Peran I, Parasido E, Li T, Simbulan-Rosenthal CM, Rosenthal D, Medvedev AV, Makarov SS, Albanese C, Byers SW, Dakshanamurthy S. Ecotoxicol Environ Saf 233 113330 (2022)
  80. Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies. Cao H, Li X, Zhang W, Wang L, Pan Y, Zhou Z, Chen M, Zhang A, Liang Y, Song M. Arch Toxicol 92 1471-1482 (2018)
  81. Differential effects of TR ligands on hormone dissociation rates: evidence for multiple ligand entry/exit pathways. Cunha Lima ST, Nguyen NH, Togashi M, Apriletti JW, Nguyen P, Polikarpov I, Scanlan TS, Baxter JD, Webb P. J Steroid Biochem Mol Biol 117 125-131 (2009)
  82. Similarities and Distinctions in Actions of Surface-Directed and Classic Androgen Receptor Antagonists. Suh JH, Chattopadhyay A, Sieglaff DH, Storer Samaniego C, Cox MB, Webb P. PLoS One 10 e0137103 (2015)
  83. The T850D Phosphomimetic Mutation in the Androgen Receptor Ligand Binding Domain Enhances Recruitment at Activation Function 2. Helsen C, Nguyen T, Vercruysse T, Wouters S, Daelemans D, Voet A, Claessens F. Int J Mol Sci 23 1557 (2022)
  84. DeepAR: a novel deep learning-based hybrid framework for the interpretable prediction of androgen receptor antagonists. Schaduangrat N, Anuwongcharoen N, Charoenkwan P, Shoombuatong W. J Cheminform 15 50 (2023)
  85. Identification of an Evolutionarily Conserved Allosteric Network in Steroid Receptors. Dube N, Khan SH, Sasse R, Okafor CD. J Chem Inf Model 63 571-582 (2023)
  86. Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs. Li F, Song C, Zhang Y, Wu D. Acta Biochim Biophys Sin (Shanghai) 54 12-24 (2022)
  87. Structure-Based Study to Overcome Cross-Reactivity of Novel Androgen Receptor Inhibitors. Radaeva M, Li H, LeBlanc E, Dalal K, Ban F, Ciesielski F, Chow B, Morin H, Awrey S, Singh K, Rennie PS, Lallous N, Cherkasov A. Cells 11 2785 (2022)
  88. Study of novel androgen receptor V770 variant in androgen insensitivity syndrome patients reveals the transitional state of the androgen receptor ligand binding domain homodimer. Helsen C, Rocca MS, Nguyen TT, Eerlings R, Lee XY, De Block S, Vinanzi C, Di Millo F, Giagulli V, Voet A, Ferlin A, Claessens F. Protein Sci 32 e4599 (2023)
  89. A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance. Alegre-Martí A, Jiménez-Panizo A, Martínez-Tébar A, Poulard C, Peralta-Moreno MN, Abella M, Antón R, Chiñas M, Eckhard U, Piulats JM, Rojas AM, Fernández-Recio J, Rubio-Martínez J, Le Romancer M, Aytes Á, Fuentes-Prior P, Estébanez-Perpiñá E. Sci Adv 9 eade2175 (2023)
  90. A partially open conformation of an androgen receptor ligand-binding domain with drug-resistance mutations. Doamekpor SK, Peng P, Xu R, Ma L, Tong Y, Tong L. Acta Crystallogr F Struct Biol Commun 79 95-104 (2023)
  91. Anti-Alopecia Activity of Coumarin Derivatives Isolated from Merremia peltata Leaves and Computational Study of Their Binding to Androgen Receptors Using Molecular Docking and Molecular Dynamic Simulation. Abdurrahman S, Ruslin R, Hasanah AN, Ifaya M, Mustarichie R. Pharmaceuticals (Basel) 16 669 (2023)
  92. Anticancer Activity and Molecular Targets of Piper cernuum Substances in Oral Squamous Cell Carcinoma Models. Machado TQ, Lima MED, da Silva RC, Macedo AL, de Queiroz LN, Angrisani BRP, da Fonseca ACC, Câmara PR, Rabelo VV, Carollo CA, de Lima Moreira D, de Almeida ECP, Vasconcelos TRA, Abreu PA, Valverde AL, Robbs BK. Biomedicines 11 1914 (2023)
  93. Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor. Noddings CM, Johnson JL, Agard DA. Nat Struct Mol Biol 30 1867-1877 (2023)
  94. ER/AR Multi-Conformational Docking Server: A Tool for Discovering and Studying Estrogen and Androgen Receptor Modulators. Wang F, Hu S, Ma DQ, Li Q, Li HC, Liang JY, Chang S, Kong R. Front Pharmacol 13 800885 (2022)
  95. New Sites for Old Suspects: Environmental Allosteric Modifiers of Nuclear Hormone Receptors. Asare B, Rajnarayanan R. J Pharmacol Clin Toxicol 3 3-1047 (2015)
  96. Prenatal Diagnosis of Twin Fetuses with a Novel AR Gene Mutation in a Chinese Family of Complete Androgen Insensitivity Syndrome. Wu W, Geng Q, Liu Y, Xu Z, Li P, Xie J. Fetal Pediatr Pathol 36 432-436 (2017)


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