The INPHARMA method (see Figure 10) was designed to determine the relative orientation between two competitive ligands in the receptor-binding pocket through the observation of inter-ligand NOE between the two ligands. It is a tr-NOE in nature as it is mediated by the bound conformation of the competing ligands and in exchange with the receptor protein. The first example was competitive binding and observation of inter-ligand NOE between baccatin III and epothilone A in the presence of tubulin, which acts as a receptor [284]. Since the observation is on the ligand site, it provides unique advantages. The detailed conformation of a ligand-protein complex can be addressed by conventional NMR. However, it is time-consuming and demands full solving of the structure and there is also a size limitation. From that aspect, ligand-based methods are more useful. The only limiting fact is that it should fulfill all the conditions of tr-NOE explained previously in terms of dissociation constant (Kd), fast exchange regime, and proper ligand to protein ratio. Then, information on the ligand structure can be derived from tr-NOE build up as a function of mixing time. This can be readily explained using the originally proposed schematics [284]. The NOESY spectrum of a mixture of the two ligands A and B in the presence of the common receptor (T) is recorded. Under the situation that each of A and B exhibit competitive binding in a fast exchange regime with the receptor T, intermolecular tr-NOE peaks between the two ligands A and B can then be observed in the NOESY spectrum due to extensive spin diffusion. During the NOESY mixing time, the first proton of ligand A (HA) binds to receptor T, which results in transfers of magnetization from HA to HT. Subsequently, the complex AT dissociates as they fulfill the dissociation constant range, which creates the opportunity for ligand B to bind to the receptor T at the same binding site. This results in the transfer of the magnetization of HT, which had been originally coming from HA, to HB. As a result, an inter-molecular correlation HA–HB can be seen, and this inter-molecular NOE will be a function of mixing time as described above. The detailed analysis of such intermolecular NOE peaks helps in assessing the relative orientation of each ligand in the binding pocket.