Fragment Based Drug Discovery

The jest of finding new drug is often eclipsed by unpredictable and uncontrollable aspects of drug designing. Basically, there are two approaches that are regularly practiced :

1. Focus on a small library representing scaffolds that are known to inhibit a class of targets.
   
2. Focus on small, simple molecules – Fragments screened at high concentration to find molecules that can be developed into drugs
   

These approaches require combination of expertise from computational chemists, structural biologists, organic chemists, biologists and biophysicists.

 

FBDD utilizes biophysical techniques to screen about 1000 small fragments which lie in range of 150-250 MW. Despite of the strong theoretical aspects, the implementation is a twisted tale of rigorous quantifying fragments because more complex molecules have greater probability of mismatches.

There are two major challenges of FBDD are as stated below:

1. Lack of specialized methods to detect fragment binding
   
2. Need of efficient optimization of fragment hits.
   

But despite all kind of stigma and apprehensions attached to this approach, today almost a dozen FBDD leads targeting different protein families in different disease areas have progressed towards clinical trials. As more leads take their course to clinical trials it will be possible to access the contribution of this approach to modern medicine.

 

For further reading on the topic please refer to:

• The rise of fragment-based drug discovery (Link)
  
• Fragonomics: fragment-based drug discovery (Link)