Abstract: Disclosed is a method for producing new leads for drug candidates. The method employs a combinatorial approach for identifying high affinity ligands. The target may be unknown and/or may include one or more unknown binding sites. A method involving a combined screening and synthesis method for bi-site inhibitors is disclosed comprising: 1) determining if there is sufficient proximity between ligands binding to different sites of a target: e.g. by using spin-labelled ligands quenching can be measured with NMR if a first ligand and second allosteric ligand are in proximity 2) connecting both ligands having linkers, via in situ synthesis in the presence of the protein scaffold (e.g. target guided synthesis combined with fragment based self assembly). Click chemistry is a preferred embodiment here. Also disclosed are kits used in context of this method, leads discovered by the method and their use in drug development.