Abstract

Chemically reactive estrogen analogs are being prepared as potential affinity labeling agents for the estrogen receptor or as cytotoxic agents that will be selective for cells containing estrogen receptor. Affinity labeling agents that have high affinity for the estrogen receptor, have low affinity for non-receptor binding proteins, and are capable of reacting efficiently with the estrogen receptor, either through an electrophilic or a photoreactive function, are being synthesized. These agents will be used to label the uterine cytosol estrogen receptor, and the labeled receptor will be characterized carefully. The cytotoxic estrogens will be assayed in cell culture systems with estrogen-responsive and non-responsive cells. Antiestrogens and antiestrogen metabolites will be prepared in high specific activity, tritium-labeled form. Their interaction with the estrogen receptor in vitro and in vivo will be investigated in an attempt to discern differences between receptor complexed with agonists vs antagonists.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK015556-16
Application #
3225413
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
16
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820

  Publications

Sharma, Abhishek; Toy, Weiyi; Guillen, Valeria Sanabria et al. (2018) Antagonists for Constitutively Active Mutant Estrogen Receptors: Insights into the Roles of Antiestrogen-Core and Side-Chain. ACS Chem Biol :
Wang, Lucia; Guillen, Valeria S; Sharma, Naina et al. (2018) New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons. ACS Med Chem Lett 9:803-808
Selvaraj, Uma Maheswari; Zuurbier, Kielen R; Whoolery, Cody W et al. (2018) Selective Nonnuclear Estrogen Receptor Activation Decreases Stroke Severity and Promotes Functional Recovery in Female Mice. Endocrinology 159:3848-3859
Amzaleg, Yonatan; Ji, Jie; Kittivanichkul, Donlaporn et al. (2018) Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells. J Steroid Biochem Mol Biol 183:10-17
Chen, Karen Lee Ann; Liu, Xiaoji; Zhao, Yiru Chen et al. (2018) Long-Term Administration of Conjugated Estrogen and Bazedoxifene Decreased Murine Fecal ?-Glucuronidase Activity Without Impacting Overall Microbiome Community. Sci Rep 8:8166
Miranda, Cristobal L; Johnson, Lance A; de Montgolfier, Oriane et al. (2018) Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice. Sci Rep 8:613
Zhao, Yuechao; Laws, Mary J; Guillen, Valeria Sanabria et al. (2017) Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors. Cancer Res 77:5602-5613
Sharma, Naina; Carlson, Kathryn E; Nwachukwu, Jerome C et al. (2017) Exploring the Structural Compliancy versus Specificity of the Estrogen Receptor Using Isomeric Three-Dimensional Ligands. ACS Chem Biol 12:494-503
Martin, Anthony; Yu, Jiali; Xiong, Jian et al. (2017) Estrogens and androgens inhibit association of RANKL with the pre-osteoblast membrane through post-translational mechanisms. J Cell Physiol 232:3798-3807
Farman, H H; Wu, J; Gustafsson, K L et al. (2017) Extra-nuclear effects of estrogen on cortical bone in males require ER?AF-1. J Mol Endocrinol 58:105-111

Showing the most recent 10 out of 91 publications