This is the web service for generation and modification of the net of xenobiotics metabolism. User could define different parameters of generation.

Value (cut-off) is the probability of metabolite formation is calculated by using integrated assessment of preliminary prediction of biotransformation classes and prediction of site of modification for each of biotransformation classes. For faster and more accurate generation choose cut-off> 0.9

The detailed description of probability of metabolite formation calculation see in *.pdf file.

We use GUSAR program for calculation toxicity end-points, which are based on the log10 representation of LD₅₀ values (mg/kg) for rats with intravenous type of administration

Three methods for estimation of applicability domain (AD) of the QSAR models are used in GUSAR during the prediction of acute toxicity [Zakharov et al QSAR Modeling and Prediction of Drug-Drug Interactions. Mol. Pharmaceutics, 2016, 13 (2), 545–556.]:
similarity: the pair-wise distance between a query compound and three nearest neighbors in the training set is calculated by Pearson’s correlation coefficient in the space of the independent variables obtained after SCR (in AD if Pearson’s correlation coefficient < 0.7);
leverage (in AD if leverage for a compound < 99th percentile in the distribution of the leverage values calculated for the training set).
assessment of accuracy: the error of prediction for the three most similar compounds in the training set relative to the whole training set (in AD if RMSE3NN/RMSEtrain < 1).


Based on the metabolites acute toxicity values calculated by our method , we proposed four different methods for calculating the integrated toxicity.
Method 1. The integral toxicity is calculated as the effect of toxicity of all metabolites without taking into account toxicity of the parent compound. It is assumed that each of the parent compounds is metabolized and all its metabolites are formed with an equal probability Pi= 1/N (N is an amount of metabolites). We estimate an integral LD₅₀ value LD_M1 using the predicted LD₅₀ values for metabolites (LDi) as follows:

Method 2. The integral toxicity is calculated as the toxic effects of the parent compounds and all its metabolites. One assumes that the parent compound is not completely metabolized and would be considered together with its metabolites. We estimate an integral LD₅₀ value LD_M2 using the predicted LD₅₀ values for metabolites (LDi) and for the parent compound (LD₀) as follows:

Method 3. The integral toxicity is calculated as the toxic effects of the most toxic metabolite. One assumes that effect of the most toxic metabolite is crucial, even if it is formed in a small quantity. We estimate an integral LD₅₀ value LD_M3 as follows:

Method 4. The integral toxicity is calculated as the toxic effects of the most toxic metabolite and the parent compound. One assumes that both effects of the most toxic metabolite and the parent compound is important. We estimate an integral LD₅₀ value LD_M4 as follows: