There are several commercially available platforms for metabolite prediction, but which one is best? The answer is, it depends. In this quick video Scott explains about top considerations and the difference of the options available.

Which is the best metabolite prediction software?

How to choose the best metabolite prediction software?

Different factors will impact which metabolite prediction software is best for you and which options are available.

Top considerations around drug metabolism

Drug metabolism presents numerous challenges when progressing drug discovery projects. To prevent delays in projects you need to consider:

  1. Which enzymes are responsible for your compounds’ metabolism and which metabolites are formed
  2. How you can reduce the risk of drug-drug interactions, and
  3. How you can design new compounds with improved metabolic stability

The importance of in silico methods

You can follow traditional methods by conducting appropriate metabolism studies, but these are time-consuming and expensive. In silico methodologies provide a fast and cost-effective way to address these challenges. They may reduce the experimentation required, ultimately saving you significant time and money.

There are several commercially available platforms, including Meteor Nexus by Lhasa Limited, MetaSite developed by Molecular Discovery, and the models developed by Optibrium, which are available in StarDrop and Semeta.

How can you pick the right metabolite prediction software?

You might be asking, which metabolism prediction system is right for me? The best choice for you will be influenced by many factors, including:

  • Which deployment option you’d like
  • Other software or equipment you need to integrate with
  • The range of enzymes and species that you want to consider
  • Your budget
  • What levels of speed and accuracy you need

Comparing the performance of metabolite prediction platforms

The choice of method is important, as it will affect speed, sensitivity and precision of results. Unfortunately, the last independent published comparison of these platforms was over a decade ago (T’Jollyn et al. 2011).

It suggested MetaSite and StarDrop have similar sensitivity and precision, and Meteor to have lower precision, but higher sensitivity. We can’t accurately assess MetaSite and Meteor Nexus development in the past decade, but can definitely say that Optibrium’s models have significantly changed and expanded since then.

Our latest model performance was published in 2024 in Xenobiotica and in 2022 in the Journal of Medicinal Chemistry.

What is Meteor Nexus?

Meteor Nexus is a knowledge-based expert system that helps you identify metabolites through knowledge of metabolic transformations, while providing you with relevant supporting information. It provides a general mammalian model that covers a broad range of Phase I and Phase II metabolism. It links directly to a range of mass spec vendor software so if you’re looking to combine experimentally seen exact masses and/or mass differences, with metabolism predictions, it can improve the process of metabolite ID. As part of the Nexus suite of software from Lhasa, it also natively links to Derek Nexus, so if you’re looking to assess the toxicity of metabolites under the ICH M7 guideline, Meteor provides a seamless way of doing that.

What is MetaSite?

MetaSite uses a pseudo-docking approach to identify sites of metabolism in a target molecule, and it now covers both phase I and phase II metabolism. It enables you to predict the structure of the most likely metabolites, identify “hot spots” in a molecule, predict sites of metabolism and propose structural modifications to overcome metabolic liability. So if you’re looking to redesign metabolically unstable compounds, then MetaSite could assist you. In addition Mass-MetaSite is an extension of MetaSite that enables you to automatically identify metabolites based on MS and MS/MS fragmentation patterns of the substrates and metabolites. As with Meteor it links directly to a range of mass spec vendor software, so if you’re looking to improve your met ID process by combining predictions and mass spec data, it could prove useful.

How do StarDrop and Semeta predict metabolism?

Optibrium’s metabolism prediction models are available both within StarDrop and Semeta. They combine quantum mechanical simulations to estimate the reactivity of each potential site of metabolism, with accessibility descriptors which capture orientation and steric effects.

These models enable you to prioritise the human enzyme families and P450 isoforms that are most likely to metabolise your compounds, and to predict the sites of metabolism by human Phase I and Phase II enzymes, P450 metabolism in a range of pre-clinical species, and the resultant metabolite structures. In addition to this, it can also predict the lability of your compounds to metabolism by P450s, helping to guide the design of compounds with improved metabolic stability. So, if you’re interested in getting a precise understanding of your compound’s likely metabolism in humans, how its metabolism may differ in key preclinical species or how to redesign metabolically unstable compounds, then the models in StarDrop and Semeta could help you.

By accessing the metabolism models within StarDrop’s data visualisation and analysis environment, you can seamlessly use the results, for example, to conduct further investigation, quickly create presentations, or rapidly design new compounds.

About the author

Scott McDonald, MSc

Scott is a Business Development Manager at Optibrium, where he helps scientists make scientifically robust decisions through software solutions that enhance drug discovery and development. He works with clients to leverage Optibrium’s products.

With over 17 years of experience in the life sciences industry, Scott holds a Master’s degree in Chemistry from the University of Salford.

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