In silico Screening for Signalosome Inhibitors
Abstract
The COP9 signalosome (CSN) is involved in cell cycle regulation, possesses kinase activity (Targets: e.g. p53 and c-Jun) and is therefore an interesting therapeutic target for anti-tumor drugs. Known inhibitors of the kinase activity exhibit low binding constants. Using them a 3D similarity screening for our in-house database is performed. The superposition algorithm enables the explicit consideration of conformers reflecting the structural flexibility. Experimental tests show significant improvement of inhibition.
The COP9 signalosome (CSN) is involved in cell cycle regulation, possesses kinase activity (Targets: e.g. p53 and c-Jun) and is therefore an interesting therapeutic target for anti-tumor drugs. Known inhibitors of the kinase activity exhibit low binding constants. Using them a 3D similarity screening for our in-house database is performed. The superposition algorithm enables the explicit consideration of conformers reflecting the structural flexibility. Experimental tests show significant improvement of inhibition.
