Simulations Plus

Other than the different approaches mentioned above, commercial packages such as GastroPlus (Simulations Plus, Lancaster, CA) [19] and IDEA (LionBioscience, Inc. Cambridge, MA) [19] are available to predict oral absorption and other pharmacokinetic properties. They are both based on the advanced compartmental absorption and transit (CAT) model [20], which incorporates the effects of drug moving through the gastrointestinal tract and its absorption into each compartment at the same time (see also Chapter 22). 

GastroPlns Simulations Plus http //www.simulations-plus.com... 

There have been considerable efforts toward modeling ADME/Tox properties and the biophysical properties of molecules (see chapters 18-20, 22, 28), including numerous commercial software solutions. Simulations Plus (http //www.simulations-plus.com/) have developed GastroPlus, a product... 

The 2D model was built from a wide array of descriptors, including also E-state indices, by Simulations Plus [89], The model is based on the associative neural network ensembles [86, 87] constructed from n=9658 compounds selected from the BioByte StarList [10] of ion-corrected experimental logP values. The model produced MAE = 0.24, r = 0.96 (R. Fraczkiewicz, personal communication). 

S + Peff = Simulations Plus predicted human jejunal effective permeability S + Sw — MP = Simulations Plus predicted water solubility (known melting point) S + Sw NoMP = Simulations Plus predicted water solubility (unknown melting point)... 

All the descriptors and properties necessary to calculate J-Alert are generated by the software program QMPRPlus (Simulations Plus, Inc.). The current set of QMPRPlus computational models for biopharmaceutical properties is listed below ... 

GastroPlus, Simulations Plus, Inc., http //www.simulations-plus.com Pathway Prism, Physiome Sciences, Inc., http //www.physiome.com Physiolab, Entelos, Inc., http //www.entelos.com/... 

Fig. 15.17 Selected examples of the distribution of predicted solubilities for diversity reagents within a 2400-member library built around a common core. Solubilities were calculated using the simulations Plus QMPRPIus solubility prediction tools and expressed in mg mL . Significant number of aqueous solubility predictions below 10 lg mL was considered sufficient criteria for deselection of that diversity reagent.

II. Product Summaries Simulations Plus develops simulation and predictive modeling software for in silico compound screening and for preclinical and clinical drug development in the area of Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET). The available applications include GastroPlus, ADMET Predictor, ADMET Modeler, DDDPlus, and MembranePlus. 

Simulations Plus, Inc., 1220 W Avenue J, Lancaster, CA 93534, USA S BIO Pte Ltd, 1 Science Park Road, 05-09 The Capricorn, Singapore Science Park 2, Singapore 117528... 

Many thousands of descriptor types have been developed over the years of chemical research. This short review is not intended to summarize these efforts in detail. Todeschini and Consonni have already provided a reference book for this purpose. Commercial and academic software for generating molecular descriptors has proliferated over the recent years. Todeschini s book lists software packages known in the year 2000. Speed of calculation, descriptor quality and diversity should be considered in selecting software. For example, absorption, distribution, metabolism, excretion, toxicity (ADMET) Predictor (Simulations Plus, Inc.) works at a rate of 250,000 molecules per horn calculating 272 molecular and 44 atomic descriptors in the following categories ... 

Bolger MB. Computational methods to predict biopharmaceutical properties. A APS meeting, Indianapolis, Oct 29-Nov 2, 2000. (Internet at http //www.simulations-plus.com/pdf files/aaps 2000 report.pdf.)... 

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