Fragment Compound Database

Fragment-based drug design (FBDD) is theoretically grounded in selecting advantageous fragments for combination or extension to generate novel drug molecules with high activity. Compared to HTS, thousands of fragments can be combined into millions of drug structures, making them easier to collect and manage. Additionally, fragments feature lower molecular weight, higher solubility, and easier structural optimization, resulting in greater drug-like potential.
For complex targets such as protein-protein interactions (PPIs), binding pockets are often flat and difficult for compounds to bind; while HTS is largely ineffective here, FBDD can identify small fragments with weak binding affinity and optimize them into potent drug candidates. This approach has led to several small-molecule drugs, with 30+ in clinical trials and multiple approved drugs: Vemurafenib, Venetoclax, Erdafitinib, Pexidartinib, Ivosidenib, Enasidenib, Baricitinib, Fedratinib, Sotorasib, and Adagrasib. Given its success, FBDD is increasingly favored by drug discovery experts.