The compounds differ with functional groups added at different positions of the scaffold (Figure ). The compounds can be grouped based on their electrostatic properties (charged and non-charged), or the positions where functional groups are added. The DFG kinase motif is a conserved Asp-Phe-Gly tripeptide at the proximal end of a flexible activation loop. Two distinct conformations, DFG-in and DFG-out, are often observed in the kinase structures, which indicate the catalytic states of the kinases. There are two ROS1 x-ray structures in the protein data bank, both in an active DFG-in conformation. Janssen have obtained four crystallographic structures. All of them have a DFG-out conformation and are complexed with compounds that share the same scaffold (Figure ).