The SuperCYP website was developed as a user-friendly platform for researchers and health professionals. The navigation bar on the left side offers ‘FAQs’ or Frequently Asked Questions, for first-time users.
‘Drug search’ enables the user to search for a drug and find information on its metabolism. ‘Get Information’ leads to a table listing CYPs involved in the metabolism of the drug. Here there is also a description of possible consequences and after clicking on the drug name on the results page ‘Drug search’ enables the user to get information for compounds by means of the CAS-number or name.
The ‘ATC tree’ is the WHO classification system that classifies drugs into different groups according to anatomic site of action, their therapeutical effect and chemical structure. It is the basis for drug alternative drug recommendations. In a Java applet, the user finds a drop-down tree with major and minor branches of classification. All drugs affiliated with a minor branch are listed in a table and information on the CYP metabolism is provided.
‘Drug–drug interaction’ is the main feature of the database. It allows users to enter names of several different drugs and to check interactions between these drugs, but they also receive alternative drug options.
As an example, Omeprazol, a proton pump inhibitor, and Nebivolol, a beta-blocker, interact on the CYP level. After selecting the drugs, the database provides detailed information on drug structures and ATC group plus CAS numbers ().
Queries and results of the SuperCyp web-interface explaining the various possibilities of the ‘Drug–drug-interaction’ option with the help of two example drugs: Omeprazole and Nebivolol.
The successive ‘results’ page warns that Omeprazol has an inhibitory effect on CYP 2D6, whereas Nebivolol is a substrate. The colored background of the table illustrates this dual use of the CYP metabolism pathway. To avoid this and to optimize the drug composition, Omeprazol can be substituted with other drugs from the same ATC-group, for example Pantoprazol, achieving a comparable effect, but using another pathway.
The proposal of Pantoprazol is derived from the assumption that it does not interact with CYP 2D6. All data on the proposed drugs are provided, and the reference to related publications is given.
The ‘CYP–Drug-interaction’ allows users to browse substrates, inducers and inhibitors of a certain CYP ().
Results of the SuperCyp web-interface for CYP 2D6 explaining the functionality of the ‘CYP–drug interaction’ table.
After the user has selected a CYP from the task menu, all known relations with drugs are listed in a table. Then users can specify the relation and focus on substrates, inducers or inhibitors. Respective drugs are given in a table and combined with further information on the particular drug and all CYP interactions. References are linked to PubMed and other scientific websites or articles. The ‘Drug Info’ button is linked to the SuperDrug Database (27
), which provides a large number of more specific information on the particular drug.
‘Polymorphism’ shows single nucleotide polymorphisms for a particular CYP. All known alleles (15
) are shown and if there is a decrease or increase in activity or expression, this information is provided. Nucleotide changes and their effects, as well as enzyme activity and assay type are given with corresponding references. Some mutation entries address the protein level directly, in which cases information on SNPs may be missing. However, it is desirable to include protein data, as they provide valuable insights into structure-function relationships.
Example: For CYP11B2, which encodes the enzyme aldosterone synthase (P450aldo), no SNPs were retrieved through keyword searches. However, our mutation/gene association text mining system found 54 protein mutations in 41 PubMed abstracts, which were then added to the database. Among those, the substitution of the highly conserved arginine at position 384 by proline reportedly led to a complete loss of function of this enzyme as part of the autosomal recessively inherited disorder CMO-I deficiency in male Caucasians.
‘Alignments’ uses a structure-based alignment program to match the amino acid sequence of all CYPs. It is possible to create a multiple sequence alignment from any number of sequences or to align them with external sequences by uploading a file or entering a sequence in FASTA format. Users may also draft a convenient output with Jalview.
‘Three-dimensional structures’ displays protein structures of human CYPs. Existing structures were extracted from the PDB. Theoretical models were generated with Swiss-Model (29
) or built manually. All structures are downloadable as PDB-files and more information on the CYP is given in the box on the right side.
Clicking the ‘Browse’-button leads to a Java applet, where all CYPs are listed in a drop-down tree, ordered by main families and subfamilies. Each CYP is viewable as a model and further information on its interactions is provided.