Fourteen of the seventeen target classes show NP Clinical enhancement to varying degrees, including proteases, nuclear receptors and oxidoreductases (Table ). In contrast, aminergic Gprotein coupled receptors (GPCRs), display no Clinical compound NP enhancement, while other GPCRs and protein kinases have only marginal Clinical NP enhancement across the categories in Table . Can the diminished Clinical NP enhancements in these major classes (45% of post-2008 Clinical compounds) be explained? One possible factor at play might be the historically longestablished and highly exemplified options for the essential pharmacophores seen in both aminergic GPCR and kinase competitive inhibitors. The majority of kinase inhibitors are competitive with ATP, and kinase drug fragments have been reported to cover a very small fraction of possible hingebinder space. Kinase inhibitors frequently bind to multiple other kinases and existing kinase inhibitor libraries are commonly used to identify new kinase leads by focussed screening. Competitive aminergic GPCR antagonists have historically typically contained a common aromatic ring and a basic group, as found in endogenous agonists (e.g. dopamine, serotonin, histamine, noradrenaline), and can employ similar ligand-protein interactions within each receptor sub-class. Targets amongst the protease, oxidoreductase and nuclear receptor (including nuclear hormone receptors and transcription factors) families, which all show Clinical compound NP enhancement, are more diverse in their substrate requirements.