SuperDRUG2: A ONE STOP RESOURCE FOR APPROVED DRUGS


Frequently Asked Questions

General

The database web site can be accessed flexibly in any modern web browser that has JavaScript enabled. However, for a smoother experience, we recommend a recent version of Safari, Mozilla Firefox or Google Chrome web browser.

Approved Drug:

Any drug that currently holds marketing authorization for human or veterinary use or is approved by a drug regulatory agency for a specific purpose.


Withdrawn/Discontinued Drug:

Any drug that was banned or discontinued world-wide or just in one country. Sometimes only a particular dose or dosage form the drug is withdrawn until unless specified that it is recalled world-wide.


Small Molecule:

A small molecule is a low molecular weight (< 900 daltons) organic compound that may help regulate a biological process, with a size on the order of 1 nm. Most drugs are small molecules.


Biological Product:

A biologic(al) product is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. In SuperDrug2, we do not display the structures of biological products.


3D Conformer:

A 3D conformer is a spatial arrangement of a chemical structure (e.g. drug) in a specific orientation. 3D conformer generation is important for chemistry, drug research and QSAR and QSPR development.


Drug-drug Interaction:

A drug interaction is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together.


PRISCUS Drug:

PRISCUS drugs are potentially inappropriate medications (PIM) that carry an increased risk of adverse drug events in the elderly patient group. A list of PIMs was introduced for the German market in 2010.


Background

2D similarity of two molecules is calculated by estimating the Tanimoto coefficient. First, the molecules are converted into molecular fingerprints (bit vector representations) which are then compared to obtain a Tanimoto score (0 to 1.0) as follows:

tanimoto

where AB is the number of bits set to one in both molecules, A is the number of bits set to one in molecule A and B is the number of bits set to one in molecule B. A Tanimoto close to 1.0 indicates excellent similarity.

The 3D conformers are superimposed using the Kabsch algorithm. Based on the normalised set of atoms in a coordinate system the centres of mass for both conformers are calculated and superimposed. Then the principal axes of inertia are estimated and aligned. For every orientation a mapping of atom pairs is performed whereupon atoms are fitted to each other with the smallest possible distance. The rotation with the highest amount of mapped pairs is used for further calculations. The normalised variant with the most minimal distance is chosen if more than one rotation with the same amount of mapped atom pairs exists. For this mapping a root-mean-square-deviation (rmsd) is calculated and further optimised.

A number of pharmacokinetic parameters that cover different phases (absorption, distribution, metabolism and excretion) are considered as inputs for our pharmacokinetics model. Drug dose, elimination half-life, volume of distribution, bioavailability, time to peak, protein/lipid binding etc. are some parameters to name.


How To Use

structure search

When using the name search, please provide a drug name as input. If the drug was found in the database, we display the drug record. In case it is not found in the database, a PubChem search is performed that will fetch the molecular structure from PubChem and is used for similarity searching. This will result in five most similar drugs to the input molecule ordered by the Tanimoto coefficient values.

structure search structure search structure search structure search

One can search the database either by searching with a chemical structure or using drug names. When using the structure search feature, please use the molecule sketching tool to draw a molecule. After this, you can set the options: search type, similarity threshold and number of results to display.

structure search
show_ligands

In the 3D Superposition section, you can either superpose two drugs within the database or alternatively the users can search for a target of interest which has a known crystal structure with a ligand bound to it. To start superimposition of two drugs, you can choose any two drugs as input that will be superposed. Here the result contains the 2D structures of both the drugs chosen along with RMSD value. You can see the interactive 3D superposition of the two drugs chosen and you can toggle between hide color and show color for better understanding of the superposition.

show_ligands

In alternative search you will find the target of interest which has a known crystal structure with a ligand bound to it. You can search for targets by Gene Name, UniProt Accession and UniProt EntryName. If the target search is successful, then you could choose or provide a new drug as input that will be superposed with the ligand that is bound to the protein structure and an RMSD value will be provided along with interactive 3D visualization of the superposed molecules within the protein structure.

show_ligands show_ligands show_ligands

First, search for a drug of interest; if the database contains the simulation data for this drug, the plasma concentration versus time curve is displayed. We provide interactive options to adjust parameters such as dose of the drug or intake interval which dynamically updates the plasma levels accordingly. You can change 3 parameters on the right side of the plot.

pharmacokinetics

For example, as seen in the plot above, the drug "Topotecan" is taken one time in 24 hours. You can select the check boxes for different metabolizers provided below the plot to see changes in the plasma level of the drug.

pharmacokinetics
druginteractions1

In order to use the drug-drug interaction feature, please select at least two drugs from the dropdown selector and click add. The drugs will be added to the bottom container and on clicking the 'Check Interactions' button, a list of potential interactions are displayed in the box below. You can see a traffic light implementation on the right side box which reflects the level of known drug drug interactions. Additionally, if any of the input drugs is in the PRISCUS list or BEERS list, we display these drugs at the bottom of the result. Click the 'Clear list' button to refresh the page for a new search.

druginteractions1 druginteractions2

Disclaimer: The content of this web site is not intended to be an alternative to professional medical therapy, diagnosis or advice.