Expert, knowledge-based software for predicting metabolic fate
- Meteor Nexus uses a comprehensive, expert knowledge base to predict the metabolic fate of chemicals.
- Meteor Nexus is based on data implemented by scientists at Lhasa Limited, who continually work on the knowledge base with current biotransformation knowledge.
- Using the three different methodologies and various filtering options, Meteor Nexus can help with decision making.
Whether your industry is cosmetics, pharmaceuticals, chemicals, or you are in academia, Meteor Nexus can help you because it:
- Provides information for decision-making when there is little or no experimental metabolism data available.
- Helps to interpret data from mass spectrometry metabolism studies more quickly and accurately.
- Shows predicted biotransformation and metabolite information graphically, and shows extensive supporting data from the knowledge base.
- Covers phase I and phase II biotransformations.
- Acts as a training or learning tool by using the extensive expert knowledge in the certified Lhasa knowledge base. Working with Meteor Nexus helps you to develop more in-depth knowledge about xenobiotic metabolism.
When a structure is submitted to Meteor Nexus, it is compared to the certified Meteor knowledge base and its dictionary of biotransformations.
Meteor Nexus then predicts the first generation metabolites by using one of three reasoning methods:
- Absolute/ Relative Reasoning
- Static Scoring (Occurrence Ratio)
- Site of Metabolism (SOM) Scoring (with Molecular Mass Variance)
Read more about the three methodologies here.
Each metabolite is then analysed to predict further metabolism. The results are displayed in an interactive tree graphic along with supporting data, such as the reasoning behind each prediction, biotransformation details and metabolite path.
Meteor Knowledge Editor
Meteor Knowledge Editor allows you to browse the Lhasa certified Meteor knowledge base and capture your organisation’s knowledge from past research and make it useful and easily accessible to your current research programs.
Using Meteor Knowledge Editor, you can create and add knowledge, such as:
- Literature references
Lhasa Limited has developed a metabolism database (Lhasa Limited Metabolism Data 1.0) which is comprised of parent compounds, their experimentally observed metabolites, and the biotransformation reactions which occur.
This data has been manually curated by Lhasa scientists from a variety of sources (including, but not limited to, Drug Metabolism and Disposition, Xenobiotica, Biochemical Pharmacology, Journal of Medicinal Chemistry, Journal of Pharmacology and Experimental Therapeutics) and is comprised of more than 17,000 reactions for more than 2,000 parent compounds*.
This curated metabolism data has been used to develop two prediction methodologies implemented within Meteor Nexus; Static Scoring and Site of Metabolism Scoring.
The certified Meteor knowledge base created and supplied by Lhasa Limited contains data from published sources, as described above, and data donated by our member organisations. This data is collated, checked and verified by Lhasa scientists before being used to develop new knowledge rules and relationships. These rules and relationships are based on empirical observations that are supported by an understanding of the biotransformation mechanism or by rigorous vetting.
*As of Dec 2017
Meteor Nexus is the expert knowledge-based software for the prediction of metabolic fate in mammals. However, Meteor can also be used for unusual metabolism, metabolite elucidation via mass defect analysis, and is compatible with some mass spectroscopy software.
Meteor Nexus can be used in cases where there is evidence of unusual metabolism. For example, where an unusual biotransformation occurs when there is no precedence for it, or the biotransformations occur in an unusual combination or order (Figures 1 and 2).
In this instance, Meteor is used with the Absolute/Relative Reasoning methodology, with the aim of providing a large resulting prediction. The results can then be searched to identify the unusual biotransformation(s) and view the suggested biotransformation pathway associated.
Figure 1: The ring contraction of 2,2,6,6-Tetramethylpiperidines to 2,2-Dimethylpyrrolidines is an example of a biotransformation displaying unusual chemistry.
Figure 2: Meteor’s Dictionary contains the Biotransformation 459 which covers the above type of reaction.
Mass defect is defined as the difference between the exact mass of a compound and its integer value. For example, quetiapine has the following molecular properties:
Molecular Formula: C21H25N3O2S
Exact Mass: 383.16675
Nominal Mass: 383
Mass Defect: 383.16675 - 373 = 0.16675
One of the known active metabolites of quetiapine is 7–hydroxyquetiapine:
Molecular Formula: C21H25N3O3S
Exact Mass: 399.16166
Nominal Mass: 399
Mass Defect: 399.16166 - 399 = 0.16166
Subtracting the mass defect values of the metabolite and the parent gives the following result:
0.16166 - 0.16675 = -0.00509
Using the “Query Mass Defect” filter in Meteor Nexus with the value -0.0051 (Tolerance = 1E-5) will only display metabolites where the molecular formula change is +O or has a mass increase of +16 e.g. hydroxylation, epoxidation, or S– or N–oxidation.
Mass defect filtering is not limited to Phase I oxidative biotransformations. It can also be applied to dehydration, nitro reduction and dealkylation reactions and Phase II biotransformation such as glucuronidation (+0.0321).
In summary, filtering by mass defect is a convenient way to reduce the number of metabolites that are displayed after a prediction has been made.
This video provides an overview on Mass Defect and Mass Defect Shift, and how this can be used within Meteor Nexus.
Meteor Nexus can be used to help elucidate the likely chemical structures detected by a mass spectrometer and help predict likely metabolic pathways. Following processing of the parent compound through Meteor, a range of filters can be applied to provide a results tree that is consistent with the experimental findings.
Users can export a report from Meteor that includes details of the mass difference between the parent compound and the predicted metabolites. This report can then be used in conjunction with Mass Spec Software, to determine whether peaks in the Mass Spec could match with metabolites predicted by Meteor.
Meteor results can be used with a range of mass spec software, including those provided by the following vendors:
- Agilent Technologies
- ThermoFisher Scientific
For more information on Meteor Nexus, or to request a demonstration, please contact us.