Fragment Libraries

The fragment-based approach is now well established as an important component of modern drug discovery1,2. This method has been proven to be more versatile and beneficial over conventional HTS-driven paradigms. Unlike HTS, FBDD identifies smaller compounds, the “fragments”, which bind to different parts of a biological target. FBDD has several advantages over HTS. A primary rationale for screening fragments is that they access a broad chemical space while screening a limited number of compounds. FBDD gives a better chance for the final lead compound to have common drug-likeness parameters. Moreover, the chance of screening a compound that is a perfect match for the intended target binding site is remotely small, because so many interactions between the ligand and spatial structure of residues in active site are often involved. On the other hand there are simpler molecules (fragments) with fewer necessary interactions and thus a much better chance of orienting with the target in a favorable manner.

Life Chemicals Fragment Collection encompasses 59,000 screening compounds including 29,000 fragments in stock and 30,000 structures in tangible databases. To meet FBDD purposes and the most efficient trends in this field, Life Chemicals designed a number of unique Fragment Libraries and Fragment Cocktails for NMR screening:

General Fragment Library
Advanced Tangible Fragments
Superior Fragment Library
● Fluorine Fragment Cocktails
Fluorine Fragment Library
Bromine Fragment Library
Fsp3-enriched Fragment Library
3D Fragment Library
PPI Fragment Library
Covalent Fragments Library
Soluble Fragments with Experimental Data

fragment-libraries


Example of the hit binding mode from in silico screening of Life Chemicals Fragment Collection

References

  1. Erlanson, D. A.; McDowell, R. S.; O’Brien, T. Fragment-based drug discovery. J. Med. Chem. 2004, 47, 3463–3482.
  2. Rees, D. C.; Congreve, M.; Murray, C. W.; Carr, R. Fragment-based lead discovery. Nat. Rev. Drug Discovery 2004, 3, 660–672.