Antiobesity library

A comprehensive search for obesity-targeting molecules was conducted using established databases including ChEMBL, Google Patents, SciFinder, and Clarivate Cortellis Drug Discovery Intelligence. The process involved the following steps:

1. Reference Compound Identification: A diverse set of compounds with known or potential anti-obesity properties was extracted from the databases, focusing on molecules either registered or in clinical trials for obesity treatment.
2. Structural Characterization: The chemical structures of the identified compounds underwent thorough analysis. This included evaluation of molecular descriptors (e.g., molecular weight, logP), 2D topological features (e.g., connectivity indices), and 3D conformational properties (e.g., shape indices). This multi-dimensional analysis provided a comprehensive structural profile for each compound.
3. Similarity Evaluation: Advanced cheminformatics tools were employed to assess structural similarities between the known anti-obesity compounds and a larger database of molecules. Various metrics were utilized, including the Tanimoto coefficient for 2D fingerprints and 3D shape-based similarity measures, to identify structurally related compounds.
4. Library Generation: A focused library of potential anti-obesity compounds was created based on structural similarity to known active molecules. Importantly, compounds targeting GLP1R were deliberately excluded to ensure diversity in potential mechanisms of action and explore novel therapeutic approaches. The final library consists of molecules meeting predetermined similarity thresholds while maintaining structural diversity.

The primary objective of creating this library was to identify novel potential anti-obesity compounds that operate through mechanisms distinct from GLP1R agonism. This approach aims to address the growing obesity epidemic by exploring alternative molecular targets and pathways involved in weight regulation.

Current obesity targets include various receptors and enzymes involved in appetite regulation, energy expenditure, and lipid metabolism. By excluding GLP1R-targeting compounds, the library focuses on other promising targets such as MC4R (melanocortin 4 receptor), SGLT2 (sodium-glucose cotransporter 2), and various lipase inhibitors 13. This strategy may lead to the discovery of new therapeutic approaches with potentially fewer side effects or improved efficacy compared to existing treatments.

The ultimate goal of this library is to provide a valuable resource for further in silico screening, in vitro testing, and potential drug discovery efforts in the field of obesity treatment, potentially uncovering novel mechanisms of action and more effective therapies for this complex metabolic disorder 57.