Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery

Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery.

In fragment-based drug discovery, the weak affinities exhibited by fragments pose significant challenges for screening. Biophysical techniques are used to address this challenge, but there is no clear consensus on which cascade of methods is best suited to identify fragment hits that ultimately translate into bound X-ray structures and provide bona fide starting points for synthesis. We have be...

Fragment - based Lead Discovery

Fragment screening to predict druggability (ligandability) and lead discovery success.

F A l w i p T s a p i c c 2 e g Target druggability – ligandability It is estimated that only 1% of drug discovery projects make it to market industry-wide. There is increasing regulatory pressure for new products to show significant improvement over existing therapies. Despite genomic initiatives, only three new targets are addressed each year with synthetic drugs [1]. Late-stage failure in cl...

An Automated Microscale Thermophoresis Screening Approach for Fragment-Based Lead Discovery

Fragment-based lead discovery has proved to be an effective alternative to high-throughput screenings in identifying chemical matter that can be developed into robust lead compounds. The search for optimal combinations of biophysical techniques that can correctly and efficiently identify and quantify binding can be challenging due to the physicochemical properties of fragments. In order to mini...

Fragment-Based Lead Discovery by NMR

fragment-based lead discovery because it combines high sensitivity and robustness to loose fragment binders with unique structural resolution and throughput. Favourable applications include screening against shallow binding pockets (such as protein-protein interactions) and side-pockets outside the highly conserved active centre of the major target classes (such as protein kinases and proteases...