a) Fragment hits are identified by screening methods and/or by de-fragmentation of known inhibitors or of natural substrates (such as an ATP mimetic, a metal chelating group, a phospho-Tyrosine mimetic, etc.). b) SAR studies, including possibly structural information, are performed with a selected fragment hit to provide suggestions on a suitable position to place a linker to be used for synthesis of the POS library. c) The optimized fragment is introduced into the POS combinatorial library to be tested using the HTS by NMR strategy.