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Need of technology for effective drug repurposing

by Sudhir Kulkarni on August 2nd, 2011

drug repositioning

Drug re-purposing is a well known route used by pharmaceutical companies to bring new product(s) in the market by using existing information of the known product. The benefits of drug re-purposing are: lesser requirements for non-clinical studies, faster reach to market, effective re-use of existing information, etc.

There are several ways in which indications for re-purposed products are identified. The most well known path is to find out other indications or disease pathways in which original target make impact. This type of drug re-purposing is known as ‘line extension’ and several examples of this kind exist. The most challenging drug re-purposing is to identify new target(s) for existing drug which is known to make significant impact on disease pathways.  There are several experimental approaches reported to identify novel targets of existing drugs, such as high throughput screening, cell based assays to screen test molecule against know protein targets and many more. However, these approaches are not comprehensive enough to ensure that all potential targets have been screened and researcher has not missed any opportunity. Computational technologies provide such comprehensive screening of therapeutic targets.

For computational technologies to provide reliable and comprehensive results and thereby offer new product development opportunities, one requires well thought out information base as well as seamless technology that does not require manual intervention. The information base for such computational technology will consist of comprehensive listing therapeutic targets involved in various diseases. Further, this will require information about structure of these therapeutic targets either from X-ray, NMR or via molecular modeling. The information base would also require knowledge of existing ligands with activities for these therapeutic targets. These ligands can be docked in to respective targets to validate the docking procedure as well as to understand interactions of residues with ligands. This information creates base for further high-throughput docking of drugs in various therapeutic targets. One also requires database of approved drugs with corresponding low energy conformers. Once all above information is collected, the high throughput docking of drugs in various therapeutic targets is preformed and activities of drugs which bind to targets are predicted. The success of such docking largely depends upon how accurately pose of drug in target is determined and how accurately it is ranked with respect to existing ligands for the target. Further, such docking will require automated technology to submit computational tasks, organize it and classify useful results from others. After compiling results of targets where drug has demonstrated putative binding, a list of most promising targets for the drug can be obtained.

Thus, computational technology can provide excellent first level screening (hypothesis) before doing detailed experimental validation of hypothesis. Have a look at this case study on one of the pharmaceutical company we worked with.

Sudhir Kulkarni

I am theoretical and computational chemist. Working as Vice-President, Discovery at VLife Sciences Technologies Pvt. Ltd. I am closely associated with technology devevelopment for computer aided drug discovery and drug repurposing. My areas of interest are computational method development, diabetic complications and cancer. In addition, I have interest in organometallic chemistry, qunatum chemistry and weak molecular interactions.

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2 Comments
  1. Karanam permalink

    Drug re-purposing is surely very exciting field.

    One can also look forward for a day, when this technology(mentioned in the blog) is routinely applied in drug discovery not only to find new therapeutic areas for existing drugs, but also to estimate the side – effect profile of an NCE. This will make drug discovery more rational.

  2. Thanks Sudhir – I very much like the the generation of new data, which helps considerably in the protection of the IP around a reprofiling project. Our company (Celentyx Ltd) follows another reprofiling strategy that also generates new data as well as identifying directly the therapeutic potential for the new indication. Celentyx has helped a number of pharmaceutical companies reprofile (repurpose) their drugs. Whilst many repositioning strategies rely primarily on mining the literature and databases for therapeutically useful responses of known drugs, Celentyx Ltd hunts for drug impact upon human immune cells. In particular a differential impact across resting, activated and pathological human immune cell types encourages greater investigation. Integral to the strategy is the investigation of key immune cell subsets at the highest levels of resolution (e.g. Tregs, Th17s, Th22s, naive & memory B cells, Bregs) that although often present in miniscule fractions of the total immune cell population, orchestrate considerable influence upon the immune system with relevance to inflammation, allergy and autoimmunity (to name just three). As mentioned above, this strategy creates clear inventive step facilitating patent protection of projects, which in our experience increases considerably the commercial potential of a reprofiled drug project. If anyone wishes to discuss reprofiling of their drugs, please contact Celentyx (contact details on the website; http://www.celentyx.com).

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