Meteor

Meteor, developed by Lhasa Limited, is an in silico software solution designed to help drug discovery and development scientists confidently assess the metabolic fate of chemical substances. By applying expert-written rules to predict biotransformations, Meteor generates a comprehensive metabolic tree of potential degradation products, enabling researchers to understand metabolite exposure, identify structural alerts, and make informed decisions earlier in the drug development process. Metabolic understanding at this stage can save significant time and improve late-stage drug survival rates.

Meteor is intended for use by scientists working in pharmaceutical research, impurity qualification, and regulatory submissions. It can be used as a standalone tool or in combination with Derek Nexus, Lhasa's expert knowledge-based toxicity prediction software, to provide an integrated workflow covering both metabolic fate prediction and toxicological assessment of metabolites and parent compounds.

Core Capabilities of Meteor

• Metabolite identification: In-depth knowledge of metabolic transformations and filtering options within Meteor help with structure elucidation of experimentally observed metabolites, supporting researchers in characterising metabolic pathways.
• Phase I and Phase II biotransformation prediction: The software applies expert-written rules to predict both Phase I and Phase II biotransformations, generating a metabolic tree of potential degradation products from a query structure.
• Filtering and prioritisation: Predicted metabolites can be filtered based on their likelihood of formation or focused on specific pathways relevant to a given study, helping researchers prioritise compounds for further investigation.
• Detailed supporting evidence: Meteor metabolic fate predictions are clearly presented and include detailed supporting evidence associated with each predicted biotransformation, providing transparency and scientific rigour.
• Integration with Derek Nexus: With a single click, predicted metabolites can be sent to Derek Nexus for toxicity and mutagenicity screening, enabling early identification of potential toxicological endpoints such as mutagenicity, carcinogenicity, or skin sensitisation.

Recommended Workflow for Metabolite Analysis

1. Define the parent compound: Enter the query structure into Meteor via SMILES, Molfile, or a drawing tool. This serves as the starting point for both metabolic and toxicological assessment.
2. Predict metabolic pathways: Run the structure through Meteor. The software applies expert-written rules to generate a metabolic tree of potential Phase I and Phase II degradation products.
3. Identify metabolites of interest: Review the predicted metabolites and apply filters based on likelihood of formation or pathway relevance to focus on the most scientifically significant structures.
4. Launch toxicity assessment: Send selected metabolites to Derek Nexus with a single click to screen for potential toxicological endpoints including mutagenicity, carcinogenicity, and skin sensitisation.
5. Compare and interpret results: Review the integrated report comparing Derek Nexus results for the parent compound against its metabolites to determine whether any metabolites or intermediates require further experimental investigation.

Derek Nexus Integration Highlights

• Over 40 years of SAR knowledge for mutagenicity: Derek Nexus contains well-established Structure-Activity Relationship (SAR) knowledge for the mutagenicity endpoint, derived from both public and proprietary data sources and regularly updated as new data becomes available.
• Negative predictions for bacterial in vitro mutagenicity: Derek Nexus streamlines the expert review process by providing negative predictions for bacterial in vitro mutagenicity, with an interpretable method to determine the reliability of a negative prediction when assessing impurities under the ICH M7 guideline.
• ICH M7 expert review support: Transparent, scientifically robust predictions supported by high-quality curated data with extensive chemical space coverage permit rapid expert review. Derek Nexus can be used in tandem with Sarah Nexus and Vitic to assign an ICH M7 classification for impurities of an Active Pharmaceutical Ingredient (API).

Regulatory Frameworks Supported

• ICH M7: Assess the potential toxicity of metabolites in the context of mutagenic impurity evaluation.
• ICH Q3A and Q3B: Determine whether an impurity is qualified for drug substances and drug products.
• ICH M3 (MIST): Determine whether further metabolite testing is required based on human metabolite exposure relative to animal toxicology studies.
• REACH (EC) 1907/2006: Support compliance with European regulation designed to protect human health and the environment from risks posed by chemical substances.

Meteor and Derek Nexus are offered by Lhasa Limited as flexible, complementary solutions that can be used independently or together depending on the scientific question, regulatory context, and existing data available. The platform is supported by a body of peer-reviewed publications and is aligned with internationally recognised regulatory frameworks for metabolite safety assessment.