eBooks & Guides

Going small to win big: Fragment-based screening in drug discovery

Issue link: https://resources.nanotempertech.com/i/1133236

Contents of this Issue

Navigation

Page 14 of 20

15 chemistry. "Bad actors" such as reactive covalent modifiers, chelators, and other types of aggregators need to be excluded or purged from the library to reduce false positives. This work is much easier and cheaper at the 1000-fold lower scale of fragment libraries. The higher hit rates that fragment screening offers, has the very important benefit of significantly expanding the classes of targets into more difficult areas, such as protein-protein interactions. Another useful characteristic of fragments that appeals to big pharma and small biotech alike is the greater solubility of the smaller compounds at the high concentrations needed to carry out the screens. The success of FBDD has already had a large impact on other drug discovery strategies. Principles of FBDD such as tight quality control of compound libraries, biophysical validation of protein-ligand interactions, and hit optimization driven by SAR have gained widespread use in drug discovery and are being applied to HTS campaigns. Big pharma companies are cleaning up their compound archives and validating hits identified using biochemical assays with biophysical methods. The future of FBDD 5 Successful use of NMR and X-ray crystallography in acquiring structural information on fragment leads bound to protein targets, has led to these techniques becoming primary screening tools for FBDD at many companies. However, their entrenched use in screening can present limitations on the types of commercially interesting targets a company might wish to pursue, because structural data using these methods may not be easily obtained in some target classes. While

Articles in this issue

view archives of eBooks & Guides - Going small to win big: Fragment-based screening in drug discovery