Covalent Fragment Library

The major limitation in fragment-based screening is the weak binding affinity of fragment hits, which not only necessitates very sensitive biophysical detection methods but also makes progressing hits to potency difficult and expensive. In particular, it requires a large compound series with typically ambiguous structure–activity relationships, because no method to date can reliably rationalize which are the dominant interactions of the original fragment. Screening covalent fragments addresses these limitations. Covalent binders are easy to detect by mass spectrometry, because the dominant interaction is unambiguous (namely, the covalent bond), which simplifies the design of follow-up series, and because the primary hits are already potent

Reaxense’s Covalent Fragment Library consists of 2,506 compounds for FBDD which are able to form covalent bonds with functional amino acid residues (such as Tyr, Ser, His, Lys, Cys) of drug targets. A subset of this library comprising only mild electrophile fragments is available separately on request.