David Lynn Phillips
Eli Lilly and Company
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by David Lynn Phillips.
The Journal of Steroid Biochemistry and Molecular Biology | 1996
Jeffrey Alan Dodge; Andrew Lawrence Glasebrook; David E. Magee; David Lynn Phillips; Masahiko Sato; Lorri L. Short; Henry U. Bryant
Representative non-steroidal estrogens, from common environmental sources such as plants, pesticides, surfactants, plastics, and animal health products, demonstrated an ability to lower serum cholesterol and prevent bone loss. Specifically, select environmental estrogens (coumestrol, genistein, methoxychlor, bisphenol A, and zeranol) effectively lowered total serum cholesterol in an estrogen-dependent animal model, the ovariectomized rat. Of these entities, coumestrol, methoxychlor, and zeranol prevented ovariectomy-induced bone loss. In an in vitro environment, these compounds competed with 17beta-estradiol for estrogen receptor binding and stimulated cell proliferation in a human breast cancer cell line (MCF-7). In addition to their well-documented effects on reproductive tissue, various environmental estrogens can dramatically affect non-reproductive parameters such as cholesterol lowering and bone metabolism.
The Journal of Steroid Biochemistry and Molecular Biology | 1997
Jeffrey Alan Dodge; Charles Willis Lugar; Stephen Cho; Lorri L. Short; Masahiko Sato; Na N. Yang; Larry A. Spangle; Michael J. Martin; David Lynn Phillips; Andrew Lawrence Glasebrook; John J. Osborne; Charles A. Frolik; Henry U. Bryant
Raloxifene (LY139481 HCl) is a selective estrogen receptor modulator (SERM) which blocks the effects of estrogen on some tissues, such as the breast and uterus, while mimicking estrogen in other tissues, such as bone. To study the origins of this unique pharmacology, we have prepared the major metabolites of raloxifene as chemical probes for examining the estrogen receptor function in vitro and in vivo. In human breast cancer cell (MCF-7) related assays, these glucuronide conjugates show little affinity for the estrogen receptor and are more than two orders of magnitude less potent at inhibiting cell proliferation than raloxifene. In non-traditional estrogen target tissue, such as bone, these metabolites are less effective than the parent at inhibiting cytokine-stimulated bone resorbing activity in rat osteoclasts or producing transforming growth factor beta-3 (TGF-beta3). In animal models, tissue distribution studies with radiolabelled metabolite indicate that conversion to raloxifene occurs readily in a variety of tissues including the liver, lung, spleen, kidney, bone and uterus. Differential conversion of metabolite in target organs, such as bone and the uterus, is not observed indicating that the origin of raloxifenes pharmacology does not result from tissue-selective deconjugation of metabolite to parent.
Bioorganic & Medicinal Chemistry Letters | 1997
Jeffrey Alan Dodge; Charles Willis Lugar; Stephen Cho; John J. Osborne; David Lynn Phillips; Andrew Lawrence Glasebrook; Charles A. Frolik
Glucuronide conjugates 1 and 2, the major metabolites of raloxifene, have been prepared and their molecular interactions with the estrogen receptor determined.
Archive | 1995
Andrew Lawrence Glasebrook; David Lynn Phillips
Archive | 1994
Henry U. Bryant; Andrew Lawrence Glasebrook; Timothy Alan Grese; David Lynn Phillips
Archive | 1993
Henry U. Bryant; Andrew Lawrence Glasebrook; Timothy Alan Grese; David Lynn Phillips
Archive | 1995
Andrew Lawrence Glasebrook; David Lynn Phillips
Archive | 1995
Andrew Lawrence Glasebrook; David Lynn Phillips
Archive | 1995
Andrew Lawrence Glasebrook; David Lynn Phillips
Archive | 1994
Henry Uhlman Bryant; Andrew Lawrence Glasebrook; Timothy Alan Grese; David Lynn Phillips