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 of the United States of America

Volumn 106, Issue 43, 2009, Pages 18114-18119

  Biggadike, Keith ^a   Bledsoe, Randy K ^b   Coe, Diane M ^a   Cooper, Tony W J ^a   House, David ^a   Iannone, Marie A ^b   Macdonald, Simon J F ^a   Madauss, Kevin P ^b   McLay, Iain M ^a   Shipley, Tracy J ^a   Taylor, Simon J ^a   Tran, Thuy B ^b   Uings, Iain J ^a   Weller, Victoria ^a   Williams, Shawn P ^b  

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

Author keywords

AlleGrow; Drug design; Glucocorticoid modulation; Intranasal glucocorticoid

Indexed keywords

2 PYRROLIDINONE AMIDE DERIVATIVE; AMIDE; ARYLINDAZOLE DERIVATIVE; BIS TRIFLUOROMETHYL ANALOGUE; D ALANINAMIDE DERIVATIVE; D PROLINAMIDE DERIVATIVE; FLUTICASONE FUROATE; GLUCOCORTICOID RECEPTOR; HORMONE RECEPTOR STIMULATING AGENT; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDAZOLE DERIVATIVE; META ACETAMIDE DERIVATIVE; PREDNISOLONE; UNCLASSIFIED DRUG;

ACCURACY; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CHEMICAL INTERACTION; COMPUTER AIDED DESIGN; COMPUTER ANALYSIS; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG DETERMINATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; HORMONAL REGULATION; HUMAN; HUMAN CELL; MALE; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; RAT; RECEPTOR OCCUPANCY; TRANSCRIPTION REGULATION; X RAY CRYSTALLOGRAPHY;

AMIDES; BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HUMANS; LIGANDS; MODELS, MOLECULAR; NF-KAPPA B; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, GLUCOCORTICOID;

EID: 70849121003     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0909125106     Document Type: Article

References (27)

1. Hench PS, Kendall EC, Slocomb CH, Polley HF (1949) The effect of a hormone of the adrenal cortex, cortisone (17-hydroxy-11-dehydrocorticosterone: compound E), and of pituitary adrenocorticotropic hormone on rheumatoid arthritis and acute rheumatic fever. Trans Assoc Am Physicians 62:64-68.
2. Avery MA, Woolfrey JR (2003) Anti-inflammatory steroids. Burger's Medicinal Chemistry and Drug Discovery, ed Abraham DJ (John Wiley, Hoboken, NJ), pp 747-853.
3. Salter M, et al. (2007) Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease. Am J Physiol Lung Cell Mol Physiol 293:L660-L667. (Pubitemid 47358828)
4. Sorbera LA, Serradell N, Bolos J (2007) Fluticasone furoate. Drugs Future 32:12-16.
5. Bledsoe RK, et al. (2002) Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 110:93-105.
6. Apolito CJ, et al. (2003). Patent WO 03/015692.
7. Biggadike K, et al. (2008) X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain. J Med Chem 51:3349-3352. (Pubitemid 351874991)
8. Schäcke H, Berger M, Hansson TG, McKerrecher D, Rehwinkel H (2008) Dissociated non-steroidal glucocorticoid receptor modulators: An update on new compounds. Expert Opin Ther Patents 18:339-352. (Pubitemid 351577865)
9. Hudson AR, Roach SL, Higuchi RI (2008) Recent developments in the discovery of selective glucocorticoid receptor modulators (SGRMs). Curr Topics Med Chem 8:750-765. (Pubitemid 351982564)
10. Mohler ML, He Y, Wu Z, Hong SS, Miller DD (2008) Dissociated non-steroidal glucocorticoids: Tuning out untoward effects. Expert Opin Ther Patents 17:37-58. (Pubitemid 46075652)
11. Miner JN, et al. (2007) Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci USA 104:19244-19249.
12. De Bosscher K, et al. (2005) A fully dissociated compound of plant origin for inflammatory gene repression. Proc Natl Acad Sci USA 102:15827-15832. (Pubitemid 41552827)
13. Cato ACB, Schäcke H, Sterry W, Asadullah K (2004) The glucocorticoid receptor as target for classic and novel anti-inflammatory therapy. Curr Drug Targets Inflamm Allergy 3:347-353. (Pubitemid 39534771)
14. Schäcke H, Docke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96:23-43. (Pubitemid 35346616)
15. Newton R, Holden NS (2007) Separating transrepression and transactivation: A distressing divorce for the glucocorticoid receptor? Mol Pharmacol 72:799-809. (Pubitemid 47481403)
16. Schäcke H, et al. (2004) Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci USA 101:227-232. (Pubitemid 38084232)
17. Takahashi H, Razavi H, Thomson D (2008) Recent progress in the discovery of novel glucocorticoid receptor modulators. Curr Topics Med Chem 8:521-530. (Pubitemid 351982593)
18. Clackers M, et al. (2007) Non-steroidal glucocorticoid agonists: The discovery of aryl pyrazoles as A-ring mimetics. Bioorg Med Chem Lett 17:4737-4745. (Pubitemid 47187714)
19. Barnett HA, et al. (2008) Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists. Bioorg Med Chem Lett 19:158-162.
20. Eldred CD, House D, Inglis GGA, Macdonald SJF, Skone PA (2006). Patent WO 06/108699.
21. Yoshikawa N, et al. (2005) The distinct agonistic properties of the phenylpyrazolosteroid cortivazol reveal interdomain communication within the glucocorticoid receptor. Mol Endocrinol 19:1110-1124. (Pubitemid 40594112)
22. Suino-Powell K, et al. (2008) Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol. Mol Cell Biol 28:1915-1923. (Pubitemid 351342623)
23. Madauss KP, et al. (2008) The first x-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist. Bioorg Med Chem Lett 18:6097-6099.
24. Biggadike K, Cooper AWJ, House D, McLay IM, Woolam GR (2007). Patent WO 07/122165.
25. Lemon BD, Freedman LP (1999) Nuclear receptor cofactors as chromatin remodelers. Current Opin Genet Dev 9:499-504.
26. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 23:3-25. (Pubitemid 27046991)
27. Ray KP, Farrow S, Daly M, Talabot F, Searle N (1997) Induction of the E-selectin promoter by interleukin 1 and TNFα and inhibition by glucocorticoids. Biochem J 28:707-715. (Pubitemid 27515620)