Fragment Library Design

3D fragments have the potential to generate new and valuable bioactive molecules

It has been estimated that there may be as many as 1063 molecules that are “drug like” and contain 30 or fewer non-hydrogen atoms. Even the largest screening libraries sample only a minute fraction of this space, reducing the chances of finding a hit compound.

Rather than screening millions of drug-like compounds, FBD sample the vast chemical space by screening a collection of small and simple molecules, with average number of non-hydrogen atoms of as few as 12. Even with small libraries of fragments (a few hundred to a thousand molecules), the likelihood of finding a hit is increased because the available chemical space is reduced as compounds become smaller.

However, the complete collection of currently available commercial compounds does not provide an even coverage of this fragment-like chemical space due to the over-representation of “flat” compounds. Fragments that populate new areas of more “three-dimensional” chemical space (such as cubanes) will potentially provide an avenue to the identification of novel and valuable bioactive molecules. Working with our industry partners, we will generate and evaluate these novel fragments.

On-going project:

  • Cubane as a 3D scaffold for fragment library construction