Figure 1.

(A) X-ray crystallographic pose of SirReal2 at the SIRT2 binding site. (B) Workflow of the study. Thirty-seven X-rays are available on the PDB. Among them, unsuitable X-rays have been removed as described. A subset of 6 PDBs was used to perform a protocol study, allowing the selection of the best screening conditions. This information was used to perform initial single conformation VS with an annotated database. Biological evaluation and further optimization led to the identification of novel scaffolds featuring SIRT2 inhibitory ability.