A deeper metabolism model

Simulations Plus gets exclusive access to Enslein Research’s CYP metabolism database

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LANCASTER, Calif.—In its continual quest to add power and functionality to its ADMET Predictor and Modeler software, Simulations Plus announced it signed an exclusive agreement with Enslein Research Inc. for the use of its database of metabolism measurement of an important group of Cytochrome P450 (CYP) enzymes that are involved in the metabolism of a broad range of drug-like molecules.

Simulations Plus first began working with Kurt Enslein, principal of Enslein Research, about a year and half ago as Enslein was beginning to explore exactly what path he would need to take for the commercialization of the data he was collecting.

"He had been collecting data and was using his own models to validate his work," says Walt Woltosz, chairman and CEO of Simulations Plus. "At that time we provided him with ADMET Modeler so we could see how his data was, to build models and determine if there might be any errors."

For his part, Enslein said that he was drawn to Simulations Plus not necessarily from a monetary perspective, but because of the quality of its modeling software. "Simulations Plus already had done this sort of thing for other endpoints," he says. "What we had done here was totally independent of Simulations Plus, using a variety of simulation approaches. When Simulations Plus got involved, the question became should I make this available using my models or could it be better using their software—because everything can always be better. Their software is very good and is very easy to use and that is how it happened."

Enslein, who some in the industry may also recognize for his work developing TOPKAT toxicity software for Accelrys, has been collecting the CYP data for a number of years under Phase 1 and Phase 2 SBIR grants. In fact, his original funding proposal was so strong that he was granted both phases at the same time, something that is very rare, Woltosz points out.

What sets the Enslein data apart is that it doesn't merely measure whether a molecule is likely to be metabolized, but the "data and models go further to estimate the rate of metabolism," Enslein says. "With an estimated rate, a scientist can decide, for example, which of two molecules that are both likely to be metabolized by a particular CYP enzyme would be better to take forward into development. Without rate, the two could appear to be equal. Having this kind of quantitative estimate should provide yet another way to eliminate problem molecules early in the discovery process."

The data from Enslein will be offered by Simulations Plus as an extra-cost "Enslein Metabolism Module" for its ADMET Predictor software. Woltosz expects interest for the add-on to be quite high, since the first version will include a predictive model for CYP3A4, considered to be one of the most prominent enzymes for human drug metabolism. Two other enzymes are also included in the first release.

Meanwhile, Enslein, located in Rochester, N.Y. continues to cull published data for new CYP enzymes, occasionally tapping students from local universities to help with his work. "This is not easy work, a lot of the published data is either incomplete or not very good, but there are a few other enzymes that look promising and I'll keep working on those."

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