Molecular and Clinical Evidence for the Unique Nature of Individual Selective Estrogen Receptor Modulators

@article{Draper2003MolecularAC,
  title={Molecular and Clinical Evidence for the Unique Nature of Individual Selective Estrogen Receptor Modulators},
  author={Michael W. Draper and William Wl Chin},
  journal={Clinical Obstetrics and Gynecology},
  year={2003},
  volume={46},
  pages={265–297}
}
  • M. Draper, W. Chin
  • Published 1 June 2003
  • Biology
  • Clinical Obstetrics and Gynecology
Strong winds of controversy are swirling around the use of hormone replacement with estrogens and progestins in the treatment of postmenopausal symptoms and conditions such as osteoporosis, cardiovascular disease, and cognition based on a number of recent large, prospective clinical studies. In this climate, it is critical to reassess the roles of estrogen and nonsteroidal partial estrogen agonist/antagonists or SERMs in the therapy of the postmenopausal woman. This paper first examines the… 
View on Wolters Kluwer
ncbi.nlm.nih.gov
4 Citations

4 Citations

Selective Estrogen Receptor Modulators: An Update on Recent Clinical Findings
TLDR
The complex function and interactions of selective estrogen receptor modulators (SERMs) are summarized to recall their suppression or initiation of target genes leading them to their actions; and explain their important roles in breast cancer treatment and possible side effects on bone, the genitourinary system, and on markers of cardiovascular risk.
Raloxifene: A Selective Estrogen-Receptor Modulator for Postmenopausal Osteoporosis – a Clinical Update on Efficacy and Safety
TLDR
The relative risk of developing breast cancer was significantly decreased in women treated with raloxifene, compared with placebo, after 4 years in MORE and 8 years in the CORE trial, a 4-year continuation of MORE.
Tamoxifen in gynaecology
A new selective estrogen receptor modulator with potent uterine antagonist activity, agonist activity in bone, and minimal ovarian stimulation.
TLDR
Data show that LY2066948 exhibits a tissue-specific profile consistent with strong antagonist activity in the uterus, agonist activity in bone, and minimal effects in the ovaries, confirming estrogen receptor agonist skeletal effects.

References

SHOWING 1-10 OF 263 REFERENCES
Selective estrogen receptor modulators: structure, function, and clinical use.
  • C. Osborne, H. Zhao, S. Fuqua
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2000
TLDR
The promising role for tamoxifen in ductal carcinoma-in-situ or for breast cancer prevention is evolving, and its use can be considered in certain patient groups.
Elucidation of the molecular mechanism of action of selective estrogen receptor modulators.
Molecular perspectives on selective estrogen receptor modulators (SERMs): progress in understanding their tissue-specific agonist and antagonist actions
Estrogens, Selective Estrogen Receptor Modulators, and Dementia: What Is the Evidence?
  • K. Yaffe
  • Psychology
    Annals of the New York Academy of Sciences
  • 2001
TLDR
The current state of knowledge of the role of estrogen for preventing dementia in postmenopausal women will be reviewed and the status of ongoing and recently completed trials of estrogen and SERMs on cognitive function or on Alzheimer's disease severity will be summarized.
Developing a SERM: Stringent Preclinical Selection Criteria Leading to an Acceptable Candidate (WAY‐140424) for Clinical Evaluation
  • B. Komm, C. Lyttle
  • Biology, Medicine
    Annals of the New York Academy of Sciences
  • 2001
TLDR
In order to develop an improved SERM, a stringent screening process was designed to select compounds that did not stimulate the uterus or breast, and under these strict conditions, WAY‐140424 was developed and, to date, the preclinical pharmacology data have accurately predicted the clinical response demonstrated in phase I and II trials.
Re: The effects of tamoxifen and estrogen on brain metabolism in elderly women.
  • J. Benson
  • Biology
    Journal of the National Cancer Institute
  • 2002
TLDR
Findings from the ATAC trial led the authors to conclude that further evaluation of the effects of aromatase inhibitors on bone mineral density and cognitive function is mandatory in order to fully assess the clinical risk–benefit ratio for these agents compared with that for tamoxifen.
Molecular mechanisms of selective estrogen receptor modulator (SERM) action.
TLDR
This model provides a basis for understanding the molecular mechanisms of SERM action, and should help identify new SERMs with enhanced tissue or target gene selectivity.
Selective estrogen receptor modulators: tissue actions and potential for CNS protection.
TLDR
This review focuses on the CNS and known neuroprotective effects of two specific SERMs, raloxifenes and arzoxifene, and suggests that ralOXifene and arZoxIfene are neuroprot protective and may preserve some elements of cognitive function.
Bazedoxifene acetate: Selective estrogen receptor modulator treatment and prevention of osteoporosis
TLDR
The structural differences between bazedoxifene and raioxifene are apparently sufficient to conter differences in their pharmacology, which supports the potential for development of more refined molecules that could achieve the optimal therapeutic target profile for a SERM.
Identification of Selective Estrogen Receptor Modulators by Their Gene Expression Fingerprints*
TLDR
Most compounds with similar GEFs had similar in vivo activities, thereby suggesting that GEF-based screens could be useful in predicting a compound's in vivo pharmacological profile.
...
...