Among the main limitations of the library predictions mentioned above are for example, having explored only one limited VKORC1 docking-cavity, water molecule contributions have not been taken into consideration, and only a limited number of threshold values have been explored. Any exploration of the vast chemical/chemotype space possibilities, including the ones reported here, will always be incomplete. For instance, the explorations did not included any in vivo physiological variables (i.e, CYP detoxification). Furthermore, once a few candidates will be more strictly defined (for instance by excluding those offtargeting other biological species in future work), those with easy chemically synthesis will have to be selected for in vivo validation. In this aspect and on due course, the identification of possible chemical synthesis pathways might be facilitated by modern retrosynthesis predictions , such as those provided by the IBM RXN server ( the above mentioned obstacles still limit the accuracy and possibilities of the predictions made here.