ADMET Predictor

ADMET Predictor, Simulations Plus Inc., http //www.simulations-plus.com (July 12, 2007). 

ADMET Predictor Constitutional, functional group counts, topological, E-state, Moriguchi descriptors, Meylan flags, molecular patterns, electronic properties, 3D descriptors, hydrogen bonding, acid-base ionization, empirical estimates of quantum descriptors 297... 

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. 

D Data Mining module utilizing the novel concept of Chemically Relevant Principal Components to visualize and analyze chemical space of results from ADMET Predictor. 

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 ... 

ADMET Predictor Simulations Plus QSPR Complete www.simulations-plus.com... 

This package from SimulationsPlus allows prediction of many of the same toxicity endpoints available in TOPKAT but employs different modeling methodology. In addition, QSTRs for estrogen receptor modulation, maximum recommended therapeutic dose, carcinogenic potency, and cardiotoxicity (hERG-encoded K+ channel affinity) are available in ADMET Predictor (,http //www.simulationsplus.com/index.html). 

Another QSAR-based commercial toxicity prediction system is Admensa Interactive (http //www.inpharmatica.co.uk/AdmensaInteractive.htm). Though primarily designed for ADME optimization, Admensa Interactive also allows for prediction of cardiotoxicity, similar to ADMET Predictor. 

All the descriptors and properties necessary to calculate ADMET Risk are generated by the software program ADMET Predictor (formerly called QMPRPlus) (Simulations Plus, Inc.). The current set of ADMET Predictor computational models for biophar-maceutical properties is listed below... 

ADMET Predictor was used to generate in silico estimates of log P, aqueous solubility, the pH of a saturated solution in water, partial charges on H-bond donors... 

Figure 17.1 Correlation of rank order for ADMET Risk and human intestinal absorption (H IA%). The ADMET Risk score ranged from 0 to 5, with 5 being compounds with the greatest risk of having poor ADMET properties. Within a single ADMET Risk number, the compounds were ranked according to ascending estimated human jejunal permeability (ADMET Predictor, Simulations Plus, Inc.). Spearman rank correlation coefficient was 0.7 (pcO.OOl).

As one part of our software validation, we tested the accuracy of GastroPlus simulation of fraction absorbed. Starting from two-dimensional structures, ADMET Predictor was used to generate the molecular descriptors and estimates of log P,... 

Multiobjective recursive partitioning N= 161 with classification for metabolism by CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4. Leave out 10%, misclassification rate 12.6%. Descriptors generated with ADMET Predictor software. 200... 

See, for example ADMET Predictor from Simulations Plus www.simulations-plus.com/products/predictor/ model plasma binding.html. 

Two software packages, ADMET predictor (Simulations plus) and ADME Boxes (Pharma Algorithms), were used to predict the potential absorption of the... 

Simulations Plus www.simulations-plus.com ADMET Predictor... 

ACD/ Percepta ADMET predictor CASE Ultra Meteor/ Derek GUSAR PASS StarDrop TOPKAT... 

The models have been updated several times (Enslein 2010). The current statistics for version 5.5 of ADMET Predictor is as follows ... 

The Enslein Model in ADMET Predictor supplies and y ax values, respectively, in units of pM and nmol min runoP P450. For user convenience, V ass. is converted into units of nmol min mg microsomal protein (human liver) and into metabolic intrinsic clearance units of pL min mg microsomal protein. The conversion factors were obtained from Inoue et al. (2006). The Enslein Metabolism Module was used to predict and y, values for the hydroxylation of 15 pyrethroids... 

In studies involving intact microsomes, the in vitro Pniax. in nmol min mg of microsomal protein is multiplied by mg of microsomal protein g of liver and by g of liver kg of body weight to obtain the in vivo value. A number of the Pniax values were out of the range of the QSAR model. No pyrethroids were used in Enslein s training sets. Pyrethroid and Tmax values may be added to the Enslein model to improve predictability. In the ADMET Predictor, y ax values were expressed in nmol min nmol of rCYP. The values were also available (calculated) in nmol min mg of microsomal protein. 

Predicted values, ADMET Predictor version 5.5, Simulations-Plus, Inc. Accmding to ADMET Predictor none of the pyiethroids were substrates of CYP 1A2... 

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