The application of an existing optimised compounds to a new disease indication

Drug repurposing is the application of an existing optimised compounds to a new disease indication. Repurposing is a pragmatic position given the substantial cost and time required for a de novo drug development.

It is known that despite a majority of compounds deemed safe, less than 15% of the compounds that enter clinical trial receive approval and this is besides the fact that a very large number of compounds never reach clinical trail stage at all.

Drug repositioning has helped to mitigate failures in drug discovery and has been associated with therapeutic breakthroughs. For example, the thalidomide medicine that had deleterious effects in the past has found a new indication. This is a growth opportunity that brings value to society.

By adopting a Drug Repositioning business model, several companies have shortened the drug development time and advanced rapidly into initial human safety testing.

Another notable drug that failed as an antihypertensive drug and was later repositioned successfully was Viagra (sildenafil). Although human clinical studies did not demonstrate the desired antihypertensive effect, “side-effects” were noted by scientists who then repositioned it as an erectile dysfunction drug.

Other examples of successfully repositioned drugs include anticancer drug Gemzar (gemcitabine) which was originally developed as an antiviral agent, and Evista (raloxifene) which was originally developed as a birth control drug, then repositioned as a successful osteoporosis drug, and later, another indication as a prophylactic for the prevention of breast cancer.

Researchers at Koru are curating and verify compounds that are currently being tested against disease models to find new uses of these molecules. Our molecules come from FDA approved drugs, clinical trial and pre-clinical compounds.

Experiment based repurposing

  • Binding affinity approach
  • Phenotypic screening

Identifying and characterizing targets druggable with small molecules is a key starting point for drug design and development.

Computational Virtual screening and HIT identification

  • Knowledge based
  • Target / molecular
  • Pathway mapping
  • Target mechanism
  • Machine learning
  • Genetic association
  • Signature based
  • Text mining and sematic approach
  • Machine learning

Koru uses a compound library to perform Virtual screening and Hit identification in traditional structure-based drug design methodologies. The diverse qualitative and quantitative SAR data points around each compound provide the brickwork to build complex workflows including fragment-based, ligand-based and high-throughput screening.