Drug repurposing involves identification of additional/new indications for a clinically approved drug or a clinical candidate. A successful drug re-purposing attempt depends on the knowledge of knowing how drugs can modulate the diseases (e.g. side effects) or their targets (e.g. polypharmacology of drugs). We at Molecular Connections develop, explore multiple data sources to extract entities related to a drug.
Molecular Connections’ custom workflows specifically designed for Drug repurposing combines the core entities of drugs’ Mechanism of Action (MoA) space by linking the chemistry and pharmacology of the drug with the biomolecular pathways and therapeutic indications. The workflows can adapt a multi-pronged approach for drug-repurposing, which can be based on:
Drug Similarity : 2D/3D structural features of drugs already approved for an indication can be used to identify drugs developed for a different indication – sharing similar structural features/side-effect profiles /target profiles.
Polypharmacology profile : network of therapeutic targets and small molecule inhibitors to identify new therapeutic opportunities for existing drugs.
Gene – expression profile : comparison of gene-expression profiles of normal and the diseased phenotype.
Side – effect based : looking for compound side effects and look for new indications within the side effect profile.
Interactome : identifying interacting proteins and other targets through protein interaction.
Molecular pathways : implication of the molecular pathway targeted by the drug in another indication.
Select Case Studies
- Exploring the role of Histone deacetylases (HDACs) in Neoplasms and use of their inhibitors in cancer treatment.
In this case study we identified frequently occurring neoplasms associated with HDAC-altered expression, drugs being used as HDAC inhibitors, and the processes encompassed by drugs to inhibit HDAC.
- Understanding pharmacologic actions, protein interactions and toxicity studies using XTractorTM.
In this case study we extracted the pharmacological actions, protein interactions and toxicity of various drugs and we also manually curated the side-effects from the drug labels.