Chemical Validation Library and Extended Validation Library

The Chemical Validation Library (CVL) (~400 compounds) and the Extended Validation Library (EVL) (~2000 compounds) are built around the same >110 selected core structures and more than 500 scaffolds with proven kinase inhibitory activity on various kinase targets.

Novel kinase targets can be validated chemically using the Chemical Validation Library compounds. Besides molecular biological target validation, chemical validation has become also very important considering the network signaling and the multiple target approach.

The novel kinase targets shall be tested first against the CVL and EVL. The resulting hits, which are typically also biologically and chemically validated, will provide sufficient input for a successful computer assisted rational design of new analogues. CVL and EVL are based on the concept that the number of kinases, we were able to identify inhibitors against, is continuously increasing and it is necessary to include more analogs around the once proven kinase inhibitor leads (EVL) in order to increase chemical diversity.

As part of the NCL we have developed an allosteric kinase inhibitory and modulatory library based on published allosteric kinase inhibitors and allosteric modulatory compounds. The allosteric kinase inhibitory library contains more than 2000 compounds.

Analysis of a big series of kinase-inhibitor complexes with high-resolution x-ray structures in PDB revealed more than 30 distinct binding modes for a large series of scaffolds, which demonstrates the importance of the use of many scaffolds for hit finding against a particular kinase.