Research Topics
| Heather A HarrisSummaryAffiliation: Wyeth Research Country: USA Publications
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Detail Information
Publications
Preclinical characterization of selective estrogen receptor beta agonists: new insights into their therapeutic potentialH A Harris
Wyeth Research, Women's Health Research Institute, 500 Arcola Rd, RN-3163, 19426 Collegeville PA, USA
Ernst Schering Found Symp Proc 1:149-61. 2006..These applications include inflammatory bowel disease, rheumatoid arthritis, endometriosis, and sepsis. This manuscript will summarize illustrative data for three ERbeta selective agonists, ERB-041, WAY-202196, and WAY-200070...- Estrogen receptor-beta: recent lessons from in vivo studiesHeather A Harris
Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, Pennsylvania 19426, USA
Mol Endocrinol 21:1-13. 2007..The next phase of research will focus on elucidating, at a molecular level, how ERbeta exerts these diverse effects and exploring the clinical utility of ERbeta-selective agonists... - Development of an early biomarker for the ovarian liability of selective estrogen receptor modulators in ratsHeather A Harris
Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, PA 19426, USA
J Steroid Biochem Mol Biol 112:40-6. 2008..We found that the degree of brain exposure correlated very well with Cyp17a1 expression... - A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosisHeather A Harris
Women s Health Research Institute, Wyeth Research, Collegeville, PA 19426, USA
Hum Reprod 20:936-41. 2005..Because endometriosis is now thought to be, at least in part, an inflammatory disease, we evaluated ERB-041's activity in an experimentally induced model of endometriosis... - Evaluation of an estrogen receptor-beta agonist in animal models of human diseaseHeather A Harris
Women s Health Research Institute, RN 3256, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA
Endocrinology 144:4241-9. 2003..These data suggest that one function of ERbeta may be to modulate the immune response, and that ERbeta-selective ligands may be therapeutically useful agents to treat chronic intestinal and joint inflammation... - ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivityRichard E Mewshaw
Chemical and Screening Sciences, Wyeth Research, Collegeville, Pennsylvania 19426, USA
J Med Chem 48:3953-79. 2005..One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases... - Structure-based design of estrogen receptor-beta selective ligandsEric S Manas
Department of Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA
J Am Chem Soc 126:15106-19. 2004.... - Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivityBarry S Komm
Wyeth Research, Women s Health Research Institute, Collegeville, Pennsylvania 19426, USA
Endocrinology 146:3999-4008. 2005..Controlled clinical trial data will be needed to confirm these effects... - Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligandsMichael S Malamas
Department of Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
J Med Chem 47:5021-40. 2004..These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions... - Estrogen receptor ligands: design and synthesis of new 2-arylindene-1-onesRobert E McDevitt
Department of Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
Bioorg Med Chem Lett 15:3137-42. 2005..Several compounds exhibited high potency and moderate selectivity for the ERbeta receptor. X-ray and modeling studies were used to understand ligand binding orientation and observed affinity... - Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activityChristopher C Chadwick
Women's Health Research Institute and Departmens of Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Proc Natl Acad Sci U S A 102:2543-8. 2005..Our results indicate the potential utility of pathway-selective ER ligands such as WAY-169916 in the treatment of chronic inflammatory diseases... - Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary glandJudy S Crabtree
Endocrinology and Reproductive Disorders Division, Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, PA 19426, USA
Mol Cell Endocrinol 287:40-6. 2008.... - Development of a mouse model of mammary gland versus uterus tissue selectivity using estrogen- and progesterone-regulated gene markersJudy S Crabtree
Endocrinology and Reproductive Disorders Division, Women s Health and Musculoskeletal Biology, Wyeth Research, 500 Arcola Road, RN2210, Collegeville, PA 19426, USA
J Steroid Biochem Mol Biol 101:11-21. 2006.... - Global transcription profiling of estrogen activity: estrogen receptor alpha regulates gene expression in the kidneyScott A Jelinsky
Genomics Department, Wyeth Research, Cambridge, Massachusetts 02140, USA
Endocrinology 144:701-10. 2003.... - Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary glandBryan J Peano
Department of Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, Pennsylvania 19426, USA
Endocrinology 150:1897-903. 2009.... - ERbeta ligands. Part 5: synthesis and structure-activity relationships of a series of 4'-hydroxyphenyl-aryl-carbaldehyde oxime derivativesRichard E Mewshaw
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem Lett 17:902-6. 2007..An X-ray co-crystal of structure 11 revealed that the oxime moiety was mimicking the C-ring of genistein, as previously predicted by SAR and docking studies... - ERbeta ligands. Part 2: Synthesis and structure-activity relationships of a series of 4-hydroxy-biphenyl-carbaldehyde oxime derivativesCuijian Yang
Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem 12:2553-70. 2004..The most potent compounds in this study had IC50 values in a radioligand binding assay of between 8-35 nM. Among the most selective compounds were 6i and 6s (49- and 31-fold ERbeta selective, respectively)... - Characterization of the biological roles of the estrogen receptors, ERalpha and ERbeta, in estrogen target tissues in vivo through the use of an ERalpha-selective ligandHeather A Harris
Women s Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426, USA
Endocrinology 143:4172-7. 2002.... - Constrained phytoestrogens and analogues as ERbeta selective ligandsChris P Miller
Chemical Sciences, Wyeth Research, 500 Arcola Road, PA 19426, Collegeville, USA
Bioorg Med Chem Lett 13:2399-403. 2003..Such receptor and cell selectivity could make 6 a useful molecular probe for better understanding the role of ERbeta in mammalian physiology... - Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligandsM Merle Elloso
Cardiovascular and Metabolic Diseases, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA
J Endocrinol 185:243-52. 2005..These results demonstrate the beneficial effects of estrogen receptor ligands, in particular ERalpha-selective ligands, and may have implications in the development of therapeutic strategies for multiple sclerosis... - 7-Substituted 2-phenyl-benzofurans as ER beta selective ligandsMichael D Collini
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem Lett 14:4925-9. 2004..Such modifications led to compounds with <10 nM potency and >100-fold selectivity for ER beta... - ERbeta ligands. Part 1: the discovery of ERbeta selective ligands which embrace the 4-hydroxy-biphenyl templateRichard J Edsall
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem 11:3457-74. 2003..The synthesis and structure-activity relationships of a series of simple biphenyls is described. Optimization of the 4-hydroxy-biphenyl template led to compounds with ERbeta selectivity on the order of 20-70-fold... - A mouse model of androgenetic alopeciaJudy S Crabtree
Department of Tissue Repair, Wyeth Research, Collegeville, Pennsylvania 19426, USA
Endocrinology 151:2373-80. 2010..These mice can now be used to test new therapeutic agents for the treatment of AGA, accelerating the drug discovery process... - Molecular determinants of ER alpha and ER beta involved in selectivity of 16 alpha-iodo-7 beta estradiolRamesh A Bhat
Women s Health Research Institute, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
J Steroid Biochem Mol Biol 88:17-26. 2004..The ER beta mutant Ile373 Met behaved like ER alpha with 16 alpha IE2. The results clearly demonstrate the role of ER alpha Met421 in the ER alpha selectivity of 16 alpha IE2... - Trace LC/MS/MS quantitation of 17beta-estradiol as a biomarker for selective estrogen receptor modulator activity in the rat brainChris Petucci
Discovery Analytical Chemistry, Pfizer, Collegeville, PA 19426, USA
J Mass Spectrom 45:65-71. 2010..This biomarker assay has provided a useful screen for medicinal chemistry optimization to produce SERMs that do not interfere with negative feedback of estrogens on the brain and for biological hypothesis testing... - Organ messenger ribonucleic acid and plasma proteome changes in the adjuvant-induced arthritis model: responses to disease induction and therapy with the estrogen receptor-beta selective agonist ERB-041Maximillian T Follettie
Biological Technologies, Wyeth Research, Cambridge, Massachusetts 02140, USA
Endocrinology 147:714-23. 2006.... - Estrogen receptor beta ligands: design and synthesis of new 2-phenyl-isoindole-1,3-dionesJohn W Ullrich
Chemical and Screening Sciences Medicinal Chemistry, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem Lett 17:118-22. 2007..The design, synthesis, and biological evaluation of the 2-phenyl-isoindole-1,3-diones will be discussed. Detailed modeling studies with X-ray support were used to understand the ligand binding orientation and observed selectivity... - Estrogen receptors alpha and beta have similar activities in multiple endothelial cell pathwaysMark J Evans
Women s Health Research Institute, Collegeville, Pennsylvania 19426, USA
Endocrinology 143:3785-95. 2002..The panel of endothelial responses coupled with a selective modulator should provide a means to characterize the roles of ERalpha and ERbeta in endothelial cells in vivo... - ERbeta ligands. Part 6: 6H-Chromeno[4,3-b]quinolines as a new series of estrogen receptor beta-selective ligandsAn T Vu
Chemical and Screening Sciences Medicinal Chemistry, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem Lett 17:4053-6. 2007..A new class of estrogen receptor beta (ERbeta) ligands based on the 6H-chromeno[4,3-b]quinoline scaffold has been prepared. Several C7-substituted analogues displayed high affinity and modest selectivity for ERbeta... - ERbeta ligands. Part 4: Synthesis and structure-activity relationships of a series of 2-phenylquinoline derivativesAn T Vu
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
Bioorg Med Chem Lett 15:4520-5. 2005..The best compound, 13b, was profiled as a selective partial agonist for ERbeta at 1 muM in a cell-based transcriptional assay. Uterine weight bioassay of 13b indicated no activation of ERalpha in vivo... - Estrogenic effects of 7alpha-methyl-17alpha-ethynylestradiol: a newly discovered tibolone metabolitePeter V N Bodine
Women s Health Research Institute, Wyeth Research, Collegeville, PA 19426, USA
Steroids 67:681-6. 2002..This steroid appears to be the most potent estrogenic metabolite of tibolone identified to date, and additional studies are, therefore, warranted regarding the role of this metabolite in the biological actions of the drug... - Suppression of ligand-dependent estrogen receptor activity by bone-resorbing cytokines in human osteoblastsP V Bodine
Women s Health Research Institute, Wyeth Ayerst Research, Inc, Radnor, Pennsylvania 19087, USA
Endocrinology 140:2439-51. 1999..In summary, these data provide evidence for a potent feedback inhibition of estrogen action in human osteoblasts that is at least partly mediated by the activation of NF-kappaB... - Functional properties of a conditionally phenotypic, estrogen-responsive, human osteoblast cell lineP V Bodine
Women s Health Research Institute, Wyeth Ayerst, Radnor, Pennsylvania 19087, USA
J Cell Biochem 65:368-87. 1997..This cell line will be a valuable in vitro model for exploring some of the molecular mechanisms of estrogen action in bone... - Expression of meltrin-alpha mRNA is not restricted to fusagenic cellsH A Harris
Women s Health Research Institute, Wyeth Ayerst Research, Radnor, Pennsylvania 19087, USA
J Cell Biochem 67:136-42. 1997..We conclude that expression of meltrin-alpha mRNA is not restricted to fusagenic cells and that, in bone, the osteoblast is the major source... - Determination of rat oral bioavailability of soy-derived phytoestrogens using an automated on-column extraction procedure and electrospray tandem mass spectrometryLarry M Mallis
Wyeth Research, Discovery Analytical Chemistry, Chemical and Screening Sciences, 500 Arcola Rd RS 2402D, Collegeville, PA 19426, USA
J Chromatogr B Analyt Technol Biomed Life Sci 796:71-86. 2003..The limit of quantitation (LOQ) for each compound was 1-1000 ng/ml with each plasma sample analysis taking less than 2 min. In general the percent oral bioavailability was determined to be between 11 and 28%... - The ligand binding profiles of estrogen receptors alpha and beta are species dependentHeather A Harris
Women s Health Research Institute, Wyeth Ayerst Research, 500 Arcola Road, Radnor, PA 19087, USA
Steroids 67:379-84. 2002..We conclude from this analysis that the ability of a compound to selectively bind to a particular ER subtype can be species dependent... - Comparison of human and rat uterine leiomyomata: identification of a dysregulated mammalian target of rapamycin pathwayJudy S Crabtree
Endocrinology and Reproductive Disorders Division, Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, Pennsylvania, USA
Cancer Res 69:6171-8. 2009..These results identify dysregulated mTOR signaling as a component of leiomyoma etiology across species and directly show the dependence of uterine leiomyomata with activated mTOR on this signaling pathway for growth... - WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shockPatricia A Cristofaro
Infectious Disease Division, Memorial Hospital of Rhode Island, Brown Medical School, Providence, RI, USA
Crit Care Med 34:2188-93. 2006..To determine the effect of an estrogen receptor-beta selective agent in experimental models of systemic infection and sepsis... - Selective estrogen receptor-beta agonists repress transcription of proinflammatory genesAleksandra Cvoro
Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Reproductive Sciences, Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143 0556, USA
J Immunol 180:630-6. 2008..These compounds might represent a new class of drugs to treat inflammatory disorders... - A study of 17beta-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophyMonette M Cotreau
Discovery Translational Medicine, Wyeth Research, Cambridge, MA, United States
Maturitas 58:366-76. 2007..Current medical therapy consists of local or systemic replacement of estrogens... - An estrogen receptor-beta agonist is active in models of inflammatory and chemical-induced painLiza Leventhal
Neuroscience Discovery Research, Wyeth Research, Princeton, NJ 08543, United States
Eur J Pharmacol 553:146-8. 2006.... - Synthesis and evaluation of B-, C-, and D-ring-substituted estradiol carboxylic acid esters as locally active estrogensDavid C Labaree
Department of Obstetrics and Gynecology, and Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Med Chem 46:1886-904. 2003..Several of the esters were tested in vivo, and two, the methyl and ethyl esters of estradiol-15alpha-formate, appeared to have the requisite properties (high local and low systemic activity) of superior "soft" estrogens...