Heather A Harris

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi Preclinical characterization of selective estrogen receptor beta agonists: new insights into their therapeutic potential
    H A Harris
    Wyeth Research, Women s Health Research Institute, 500 Arcola Rd, RN 3163, 19426 Collegeville PA, USA
    Ernst Schering Found Symp Proc . 2006
  2. ncbi Estrogen receptor-beta: recent lessons from in vivo studies
    Heather A Harris
    Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, Pennsylvania 19426, USA
    Mol Endocrinol 21:1-13. 2007
  3. doi Development of an early biomarker for the ovarian liability of selective estrogen receptor modulators in rats
    Heather A Harris
    Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, PA 19426, USA
    J Steroid Biochem Mol Biol 112:40-6. 2008
  4. ncbi A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis
    Heather A Harris
    Women s Health Research Institute, Wyeth Research, Collegeville, PA 19426, USA
    Hum Reprod 20:936-41. 2005
  5. ncbi Evaluation of an estrogen receptor-beta agonist in animal models of human disease
    Heather A Harris
    Women s Health Research Institute, RN 3256, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA
    Endocrinology 144:4241-9. 2003
  6. ncbi ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity
    Richard E Mewshaw
    Chemical and Screening Sciences, Wyeth Research, Collegeville, Pennsylvania 19426, USA
    J Med Chem 48:3953-79. 2005
  7. ncbi Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands
    Michael S Malamas
    Department of Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    J Med Chem 47:5021-40. 2004
  8. ncbi Structure-based design of estrogen receptor-beta selective ligands
    Eric 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
  9. ncbi Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity
    Barry S Komm
    Wyeth Research, Women s Health Research Institute, Collegeville, Pennsylvania 19426, USA
    Endocrinology 146:3999-4008. 2005
  10. ncbi Estrogen receptor ligands: design and synthesis of new 2-arylindene-1-ones
    Robert 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

Collaborators

Detail Information

Publications43

  1. ncbi Preclinical characterization of selective estrogen receptor beta agonists: new insights into their therapeutic potential
    H A Harris
    Wyeth Research, Women s Health Research Institute, 500 Arcola Rd, RN 3163, 19426 Collegeville PA, USA
    Ernst Schering Found Symp Proc . 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...
  2. ncbi Estrogen receptor-beta: recent lessons from in vivo studies
    Heather 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...
  3. doi Development of an early biomarker for the ovarian liability of selective estrogen receptor modulators in rats
    Heather 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...
  4. ncbi A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis
    Heather 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...
  5. ncbi Evaluation of an estrogen receptor-beta agonist in animal models of human disease
    Heather 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...
  6. ncbi ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene scaffold to achieve ERbeta selectivity
    Richard 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...
  7. ncbi Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands
    Michael 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...
  8. ncbi Structure-based design of estrogen receptor-beta selective ligands
    Eric 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
    ....
  9. ncbi Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity
    Barry 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...
  10. ncbi Estrogen receptor ligands: design and synthesis of new 2-arylindene-1-ones
    Robert 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...
  11. pmc Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activity
    Christopher 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...
  12. doi Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland
    Judy 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
    ....
  13. ncbi Development of a mouse model of mammary gland versus uterus tissue selectivity using estrogen- and progesterone-regulated gene markers
    Judy 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
    ....
  14. ncbi Global transcription profiling of estrogen activity: estrogen receptor alpha regulates gene expression in the kidney
    Scott A Jelinsky
    Genomics Department, Wyeth Research, Cambridge, Massachusetts 02140, USA
    Endocrinology 144:701-10. 2003
    ....
  15. doi Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland
    Bryan J Peano
    Department of Women s Health and Musculoskeletal Biology, Wyeth Research, Collegeville, Pennsylvania 19426, USA
    Endocrinology 150:1897-903. 2009
    ....
  16. ncbi ERbeta ligands. Part 5: synthesis and structure-activity relationships of a series of 4'-hydroxyphenyl-aryl-carbaldehyde oxime derivatives
    Richard 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...
  17. ncbi ERbeta ligands. Part 2: Synthesis and structure-activity relationships of a series of 4-hydroxy-biphenyl-carbaldehyde oxime derivatives
    Cuijian 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)...
  18. ncbi 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 ligand
    Heather A Harris
    Women s Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426, USA
    Endocrinology 143:4172-7. 2002
    ....
  19. ncbi Constrained phytoestrogens and analogues as ERbeta selective ligands
    Chris 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...
  20. ncbi Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligands
    M 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...
  21. ncbi 7-Substituted 2-phenyl-benzofurans as ER beta selective ligands
    Michael 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...
  22. ncbi ERbeta ligands. Part 1: the discovery of ERbeta selective ligands which embrace the 4-hydroxy-biphenyl template
    Richard 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...
  23. doi A mouse model of androgenetic alopecia
    Judy 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...
  24. ncbi Molecular determinants of ER alpha and ER beta involved in selectivity of 16 alpha-iodo-7 beta estradiol
    Ramesh 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...
  25. doi Trace LC/MS/MS quantitation of 17beta-estradiol as a biomarker for selective estrogen receptor modulator activity in the rat brain
    Chris 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...
  26. ncbi 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-041
    Maximillian T Follettie
    Biological Technologies, Wyeth Research, Cambridge, Massachusetts 02140, USA
    Endocrinology 147:714-23. 2006
    ....
  27. ncbi Estrogen receptor beta ligands: design and synthesis of new 2-phenyl-isoindole-1,3-diones
    John 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...
  28. ncbi Estrogen receptors alpha and beta have similar activities in multiple endothelial cell pathways
    Mark 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...
  29. ncbi ERbeta ligands. Part 6: 6H-Chromeno[4,3-b]quinolines as a new series of estrogen receptor beta-selective ligands
    An 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...
  30. ncbi ERbeta ligands. Part 4: Synthesis and structure-activity relationships of a series of 2-phenylquinoline derivatives
    An 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...
  31. ncbi Estrogenic effects of 7alpha-methyl-17alpha-ethynylestradiol: a newly discovered tibolone metabolite
    Peter 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...
  32. ncbi Expression of meltrin-alpha mRNA is not restricted to fusagenic cells
    H 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...
  33. ncbi Functional properties of a conditionally phenotypic, estrogen-responsive, human osteoblast cell line
    P 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...
  34. ncbi Suppression of ligand-dependent estrogen receptor activity by bone-resorbing cytokines in human osteoblasts
    P 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...
  35. ncbi Determination of rat oral bioavailability of soy-derived phytoestrogens using an automated on-column extraction procedure and electrospray tandem mass spectrometry
    Larry 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%...
  36. ncbi The ligand binding profiles of estrogen receptors alpha and beta are species dependent
    Heather 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...
  37. ncbi Comparison of human and rat uterine leiomyomata: identification of a dysregulated mammalian target of rapamycin pathway
    Judy 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...
  38. ncbi A study of 17beta-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophy
    Monette 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...
  39. ncbi An estrogen receptor-beta agonist is active in models of inflammatory and chemical-induced pain
    Liza Leventhal
    Neuroscience Discovery Research, Wyeth Research, Princeton, NJ 08543, United States
    Eur J Pharmacol 553:146-8. 2006
    ....
  40. ncbi WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shock
    Patricia 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...
  41. ncbi Synthesis and evaluation of B-, C-, and D-ring-substituted estradiol carboxylic acid esters as locally active estrogens
    David 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...
  42. ncbi Selective estrogen receptor-beta agonists repress transcription of proinflammatory genes
    Aleksandra 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...