Simulations Plus, Inc. (NASDAQ: SLP), a leading provider of simulation and modeling software for pharmaceutical discovery and development, has released version 5.5 of its best-in-class ADMET Predictor™ software for predicting properties of molecules with only their structures as inputs. This release includes a number of major improvements:

• A new Metabolite Module with 10 new models for sites of metabolism
• An expanded Toxicity Module with 9 new models, extending the total number to over 30
• An expanded Enslein Metabolism Module
• An expanded Physicochemical and Biopharmaceutical Properties Module
• Expanded ADMET Risk™ capabilities for multiobjective molecule design optimization
• Expanded ADMET Modeler™ model-building capabilities
• Enhanced graphics presentations for visualization of new calculated properties

Dr. Robert Fraczkiewicz, team leader for ADMET Informatics at Simulations Plus, said: “This new version of ADMET Predictor incorporates the results of two years of research and development carried out under our Small Business Innovation Research (SBIR) grant from the National Institutes of Health as well as internal funding. The first part of our SBIR effort involved building a unique capability to rapidly estimate quantum mechanical descriptors for atoms and derived molecular descriptors. This capability enables us to process hundreds of thousands of molecules in an hour on a laptop computer, while the usual quantum mechanical calculations can take as long as a day for each structure. With these and a few other atomic descriptors in hand, we have a better set of inputs to use for building predictive models. The new Metabolite Module is heavily dependent on these atomic descriptors, and their use has improved our already best-in-class predictions for many other molecular properties as well.”

Dr. Marvin Waldman, Research Fellow at Simulations Plus, said: “As chemists work to design new drug molecules, a major concern is how they will be converted by various enzymes in the body into metabolites. Knowing which enzymes are most likely to cause those changes is important because chemists want to avoid drug-drug interactions with other drugs that are metabolized by the same enzymes. Also of concern are the potential effects the metabolites will have on the body. Our new Metabolite Module enables chemists to see which atoms in a drug molecule are most likely to be attacked by certain human cytochrome P450 (CYP) enzymes, thereby changing it into a different molecule – a metabolite. New predictive models are available for 5 different CYP enzymes, known as 1A2, 2C9, 2C19, 2D6, and 3A4. Sometimes metabolites have beneficial effects, sometimes they cause adverse effects, and many times they are simply cleared out of the body with little effect. By providing chemists with a tool to let them see the most likely way potential drug molecules will be metabolized, problems can be avoided very early in drug discovery before large investments in time and money have been made in wet-lab experiments or in animal or human studies.”

Dr. Waldman continued, “The data from which the models have been built came from the Symyx Metabolite database that was obtained through an agreement we signed with Symyx last year, supplemented with significant additions made through our own literature curation efforts. Symyx was merged into Accelrys (“ACCL”) later in 2010 and the database is now known as the Accelrys Metabolite database.”

“The Accelrys Metabolite database is the most comprehensive collection of information on xenobiotic metabolism in the world, and we are very pleased to see it used by the researchers at Simulations Plus to create state-of-the-art tools for identifying CYP substrates and their sites of oxidation,” said Trevor Heritage, executive vice president of Software Products at Accelrys.

Walt Woltosz, chairman and chief executive officer of Simulations Plus, added, “The additions to this new version serve to:

• Enhance the value of ADMET Predictor for our pharmaceutical customers.
• Project ADMET Predictor further into the markets for toxicity prediction, both environmental and pharmaceutical.
• Enhance the combination of our MedChem Studio™ data mining and molecule design software through the integration of ADMET Predictor with MedChem Studio and the new powerful ADMET Risk™ capabilities.

“ADMET Predictor has been consistently ranked at the top in published independent comparison studies for predictive accuracy, and we believe that the capabilities incorporated into version 5.5 will further extend our competitive advantage. The new Metabolite Module complements our previously released Enslein Metabolism Module, which predicts the rate at which a molecule will be metabolized by the same enzymes listed above, but does not indicate where on the molecule metabolism is likely to take place.”