LGD-5552, an antiinflammatory glucocorticoid receptor ligand with reduced side effects, in vivo

Endocrinology

Volumn 149, Issue 5, 2008, Pages 2080-2089

  López, Francisco J ^a   Ardecky, Robert J ^a,c   Bebo, Bruce ^a,d   Benbatoul, Khalid ^a,e   De Grandpre, Louise ^a   Liu, Sha ^a,f   Leibowitz, Mark D ^a,b   Marschke, Keith ^a   Rosen, Jon ^a,g   Rungta, Deepa ^a   Viveros, Humberto O ^a,h   Yen, Wan Ching ^a,i   Zhi, Lin ^a   Negro Vilar, Andrés ^a,j   Miner, Jeffrey N ^a,b  

^a LIGAND PHARMACEUTICALS INC   (United States)

^b Ardea Biosciences Inc   (United States)

^c BURNHAM INSTITUTE   (United States)

^d Elbion AG   (Germany)

^e Millipore Corporation   (United States)

^f Metabasis Therapeutics Inc   (United States)

^g EXELIXIS INC   (United States)

^h Oncomed Pharmaceuticals Inc ^*  (United States)

ⁱ OncoMed Pharmaceuticals Inc   (United States)

^j Transmed Institute   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; CYTOKINE; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; INTERLEUKIN 10; LGD 5552; MONOCYTE CHEMOTACTIC PROTEIN 1; PREDNISOLONE; STEROID; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTHRITIS; ARTICLE; AUTOIMMUNE DISEASE; CONTROLLED STUDY; DOSE RESPONSE; DRUG FORMULATION; DRUG POTENCY; DRUG SYNTHESIS; ENCEPHALITIS; GENE CONTROL; GENE REPRESSION; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; HORMONE BINDING; HYPERTENSION; IC 50; IN VIVO STUDY; MALE; NONHUMAN; PAW EDEMA; PRIORITY JOURNAL; RAT;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ARTHRITIS, EXPERIMENTAL; ARTHRITIS, RHEUMATOID; BENZOPYRANS; BENZYLIDENE COMPOUNDS; CELLS, CULTURED; DRUG EVALUATION, PRECLINICAL; HUMANS; LIGANDS; MALE; MODELS, BIOLOGICAL; PREDNISOLONE; RATS; RATS, INBRED LEW; RATS, INBRED WKY; RATS, SPRAGUE-DAWLEY; RECEPTORS, GLUCOCORTICOID; SPODOPTERA; SUBSTRATE SPECIFICITY;

EID: 42449147095     PISSN: 00137227     EISSN: 00137227     Source Type: Journal    
DOI: 10.1210/en.2007-1353     Document Type: Article

References (34)

1. Rosen J, Miner JN 2005 The search for safer glucocorticoid receptor ligands. Endocr Rev 26:452-464
2. Miner JN, Hong MH, Negro-Vilar A 2005 New and improved glucocorticoid receptor ligands. Expert Opin Investig Drugs 14:1527-1545
3. Miner JN 2002 Designer glucocorticoids. Biochem Pharmacol 64:355-361
4. Schacke H, Rehwinkel H, Asadullah K 2005 Dissociated glucocorticoid receptor ligands: compounds with an improved therapeutic index. Curr Opin Investig Drugs 6:503-507
5. Herrlich P 2001 Cross-talk between glucocorticoid receptor and AP-1. Oncogene 20:2465-2475
6. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, Gronemeyer H, Resche-Rigon M 1997 Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol 11:1245-1255
7. Iwasaki K, Mishima E, Miura M, Sakai N, Shimao S 1995 Effect of RU 486 on the atrophogenic and antiinflammatory effects of glucocorticoids in skin. J Dermatol Sci 10:151-158
8. Coghlan MJ, Jacobson PB, Lane B, Nakane M, Lin CW, Elmore SW, Kym PR, Luly JR, Carter GW, Turner R, Tyree CM, Hu J, Elgort M, Rosen J, Miner JN 2003Anovel antiinflammatory maintains glucocorticoid efficacy with reduced side effects. Mol Endocrinol 17:860-869
9. Lin CW, Nakane M, Stashko M, Falls D, Kuk J, Miller L, Huang R, Tyree C, Miner JN, Rosen J, Kym PR, Coghlan MJ, Carter G, Lane BC 2002 Transactivation and repression properties of the novel nonsteroid glucocorticoid receptor ligand 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1- methylcyclohexen-3-y 1)-1H-[1]benzopyrano[3,4-f]quinoline (A276575) and its four stereoisomers. Mol Pharmacol 62:297-303
10. Hudson AR, Roach SL, Higuchi RI, Phillips DP, Bissonnette RP, Lamph WW, Yen J, Li Y, Adams ME, Valdez LJ, Vassar A, Cuervo C, Kallel EA, Gharbaoui CJ, Mais DE, Miner JN, Marschke KB, Rungta D, Negro-Vilar A, Zhi L 2007 Synthesis and characterization of nonsteroidal glucocorticoid receptor modulators for multiple myeloma. J Med Chem 50:4699-4709
11. Ardecky RJ, Hudson AR, Phillips DP, Tyhonas JS, Deckhut C, Lau TL, Li Y, Martinborough EA, Roach SL, Higuchi RI, Lopez FJ, Marschke KB, Miner JN, Karanewsky DS, Negro-Vilar A, Zhi L 2007 5(Z)-benzylidene-1,2-dihydro-9- hydroxy-10-methoxy-2,2,4-trimethyl-5H-1-aza-6-oxa-chrysenes as nonsteroidal glucocorticoid receptor modulators. Bioorg Med Chem Lett 17:4158-4162
12. DeBlasi A, O'Reilly K, Motulsky HJ 1989 Calculating receptor number from binding experiments using same compound as radioligand and competitor. Trends Pharmacol Sci 10:227-229
13. Berger TS, Parandoosh Z, Perry BW, Stein RB 1992 Interaction of glucocorticoid analogues with the human glucocorticoid receptor. J Steroid Biochem Mol Biol 41:733-738
14. Vegeto E, Allan GF, Schrader WT, Tsai MJ, McDonnell DP, O'Malley BW 1992 The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell 69:703-713
15. Jilma B, Blann AD, Stohlawetz P, Eichler HG, Kautzky-Willer A, Wagner OF 2000 Dexamethasone lowers circulating E-selectin and ICAM-1 in healthy men. J Lab Clin Med 135:270-274
16. Wehling-Henricks M, Lee JJ, Tidball JG 2004 Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophindeficient skeletal muscle. Neuromuscul Disord 14:483-490
17. Jacobson PB, Morgan SJ, Wilcox DM, Nguyen P, Ratajczak CA, Carlson RP, Harris RR, Nuss M 1999 A new spin on an old model: in vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parameters and histopathology in the adjuvant arthritic rat. Arthritis Rheum 42:2060-2073
18. Burrows GG, Bebo Jr BF, Adlard KL, Vandenbark AA, Offner H 1998 Twodomain MHC class II molecules form stable complexes with myelin basic protein 69-89 peptide that detect and inhibit rat encephalitogenic T cells and treat experimental autoimmune encephalomyelitis. J Immunol 161:5987-5996
19. Hausler A, Girard J, Baumann JB, Ruch W, Otten UH 1983 Long-term effects of betamethasone on blood pressure and hypothalamo-pituitary- adrenocortical function in spontaneously hypertensive and normotensive rats. Horm Res 18:191-197
20. Doggrell SA 2005 The nitrosterols - a step forward from the steroid antiinflammatory drugs? Expert Opin Investig Drugs 14:823-828
21. Barker M, Clackers M, Copley R, Demaine DA, Humphreys D, Inglis GG, Johnston MJ, Jones HT, Haase MV, House D, Loiseau R, Nisbet L, Pacquet F, Skone PA, Shanahan SE, Tape D, Vinader VM, Washington M, Uings I, Upton R, McLay IM, Macdonald SJ 2006 Dissociated nonsteroidal glucocorticoid receptor modulators: discovery of the agonist trigger in a tetrahydronaphthalene- benzoxazine series. J Med Chem 49:4216-4231
22. De Bosscher K, Vanden Berghe W, Beck IM, Van Molle W, Hennuyer N, Hapgood J, Libert C, Staels B, Louw A, Haegeman G 2005 A fully dissociated compound of plant origin for inflammatory gene repression. Proc Natl Acad Sci USA 102:15827-15832
23. Schacke H, Schottelius A, Docke WD, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K 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
24. de Dios A, Shih C, Lopez de Uralde B, Sanchez C, del Prado M, Martin Cabrejas LM, Pleite S, Blanco-Urgoiti J, Lorite MJ, Nevill Jr CR, Bonjouklian R, York J, Vieth M, Wang Y, Magnus N, Campbell RM, Anderson BD, McCann DJ, Giera DD, Lee PA, Schultz RM, Li LC, Johnson LM, Wolos JA 2005 Design of potent and selective 2-aminobenzimidazole-based p38α MAP kinase inhibitors with excellent in vivo efficacy. J Med Chem 48:2270-2273
25. Smith CJ, Ali A, Balkovec JM, Graham DW, Hammond ML, Patel GF, Rouen GP, Smith SK, Tata JR, Einstein M, Ge L, Harris GS, Kelly TM, Mazur P, Thompson CM, Wang CF, Williamson JM, Miller DK, Pandit S, Santoro JC, Sitlani A, Yamin TT, O'Neill EA, Zaller DM, Carballo-Jane E, Forrest MJ, Luell S 2005 Novel ketal ligands for the glucocorticoid receptor: in vitro and in vivo activity. Bioorg Med Chem Lett 15:2926-2931
26. Thompson CF, Quraishi N, Ali A, Tata JR, Hammond ML, Balkovec JM, Einstein M, Ge L, Harris G, Kelly TM, Mazur P, Pandit S, Santoro J, Sitlani A, Wang C, Williamson J, Miller DK, Yamin TT, Thompson CM, O'Neill EA, Zaller D, Forrest MJ, Carballo-Jane E, Luell S 2005 Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy. Bioorg Med Chem Lett 15:2163-2167
27. Ali A, Thompson CF, Balkovec JM, Graham DW, Hammond ML, Quraishi N, Tata JR, Einstein M, Ge L, Harris G, Kelly TM, Mazur P, Pandit S, Santoro J, Sitlani A, Wang C, Williamson J, Miller DK, Thompson CM, Zaller DM, Forrest MJ, Carballo-Jane E, Luell S 2004 Novel N-arylpyrazolo[3,2-c]-based ligands for the glucocorticoid receptor: receptor binding and in vivo activity. J Med Chem 47:2441-2452
28. Hamilton TA, Ohmori Y, Tebo J 2002 Regulation of chemokine expression by antiinflammatory cytokines. Immunol Res 25:229-245
29. Daly C, Rollins BJ 2003 Monocyte chemoattractant protein-1 (CCL2) in inflammatory disease and adaptive immunity: therapeutic opportunities and controversies. Microcirculation 10:247-257
30. Gilson H, Schakman O, Combaret L, Lause P, Grobet L, Attaix D, Ketelslegers JM, Thissen JP 2007 Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 148:452-460
31. Udden J, Bjorntorp P, Arner P, Barkeling B, Meurling L, Rossner S 2003 Effects of glucocorticoids on leptin levels and eating behaviour in women. J Intern Med 253:225-231
32. Heuck C, Heickendorff L, Wolthers OD 2000 A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide. Arch Dis Child 83:334-339
33. Owen HC, Miner JN, Ahmed SF, Farquharson C 2007 The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Mol Cell Endocrinol 264:164-170
34. McIntosh AL, Hanssen AD, Wenger DE, Osmon DR 2006 Recent intraarticular steroid injection may increase infection rates in primary THA. Clin Orthop Relat Res 451:50-54