Modeling of signaling pathways for endocrine disruptors.

The so called endocrine disruptors have become an important working hypothesis for a wide range of toxicology researchers. This hypothesis has also attracted those who have worked on designer estrogens or selective estrogen receptor modulators. Already numbers of substances have been identified as such chemicals, but there remain a large number of chemicals waiting to be tested for their endocrine modulating capabilities. Because of the time and costs required for wet lab tests, it is unrealistic to apply these kinds of tests to all such suspicious or probable chemicals. Thus some theoretical methods must be developed for this purpose. However the conventional QSAR (quantitative structure activity relationships) approach is of limited relevance to this problem, because these methods do not take detailed mechanisms of molecular interactions in biological systems into account. Thus we have developed a database complex system that enables one to trace molecular interactions triggered by interaction of receptors with xenobiotic chemicals. The main components of this database complex are a potential endocrine disruptor database, a receptor database, a cell signaling networks database, a transcription factor database, and an affinity binding database based on modes of actions.