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From our current knowledge, it is obvious that estrogen action in
volves more than reproduction and fertility. Rather, estrogens
affect and influence a number of other organ systems such as the
immune, cardiovascular and central nervous system as well as the
gastrointes tinal tract, urinary tract and skeleton. The importance
of estrogens and estrogen receptor activity is appreciated from the
spectrum of significant physiological dysfunctions that occur when
there is a loss The participants of the workshop VI Preface of the
hormone or the receptor activity. Loss of estrogen, however (for
instance during menopause), occurs with time and results in a
variety of clinical conditions. We know that the developmental loss
of estrogen, as seen in clinical cases of aromatase gene mutations
and experimental models, has dramatic effects in both men and women
alike. The evidence that these effects are mediated through the
estrogen receptor(s) is based on similar but not always identical
phenotypes as observed in experimental animal models of estrogen
receptor mutations as well as the single clinical case of an
estrogen receptor alpha mutant patient. Developing an understanding
of the spectrum of estrogen in a variety of tissues related to the
condition of estrogen loss is a major and highly active clinical as
well as basic scientific research area. Following the discovery of
a second estrogen receptor and possible receptor ligand-independent
activity as well as the genomic and non genomic actions of
estrogen, it is clear that the mechanisms of the effects of
estrogen are multifaceted.
Research in the pharmaceutical industry today is in many respects
quite different from what it used to be only fifteen years ago.
There have been dramatic changes in approaches for identifying new
chemical entities with a desired biological activity. While
chemical modification of existing leads was the most important
approach in the 1970s and 1980s, high-throughput screening and
structure-based design are now major players among a multitude of
methods used in drug discov ery. Quite often, companies favor one
of these relatively new approaches over the other, e.g., screening
over rational design, or vice versa, but we believe that an
intelligent and concerted use of several or all methods currently
available to drug discovery will be more successful in the medium
term. What has changed most significantly in the past few years is
the time available for identifying new chemical entities. Because
of the high costs of drug discovery projects, pressure for maximum
success in the shortest possible time is higher than ever. In
addition, the multidisciplinary character of the field is much more
pronounced today than it used to be. As a consequence, researchers
and project managers in the pharmaceutical industry should have a
solid knowledge of the more important methods available to drug
discovery, because it is the rapidly and intelligently combined use
of these which will determine the success or failure of preclinical
projects.
Research in the pharmaceutical industry today is in many respects
quite different from what it used to be only fifteen years ago.
There have been dramatic changes in approaches for identifying new
chemical entities with a desired biological activity. While
chemical modification of existing leads was the most important
approach in the 1970s and 1980s, high-throughput screening and
structure-based design are now major players among a multitude of
methods used in drug discov ery. Quite often, companies favor one
of these relatively new approaches over the other, e.g., screening
over rational design, or vice versa, but we believe that an
intelligent and concerted use of several or all methods currently
available to drug discovery will be more successful in the medium
term. What has changed most significantly in the past few years is
the time available for identifying new chemical entities. Because
of the high costs of drug discovery projects, pressure for maximum
success in the shortest possible time is higher than ever. In
addition, the multidisciplinary character of the field is much more
pronounced today than it used to be. As a consequence, researchers
and project managers in the pharmaceutical industry should have a
solid knowledge of the more important methods available to drug
discovery, because it is the rapidly and intelligently combined use
of these which will determine the success or failure of preclinical
projects.
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