Data structures for compound promiscuity analysis: promiscuity cliffs, pathways and promiscuity hubs formed by inhibitors of the human kinome

Aim: A large collection of promiscuity cliffs (PCs), PC pathways (PCPs) and promiscuity hubs (PHs) formed by inhibitors of human kinases is made freely available. Methodology: Inhibitor PCs were systematically identified and organized in network representations, from which PCPs were extracted. PH compounds were classified and their neighborhoods analyzed. Data & exemplary results: Nearly 16,000 PCs covering the human kinome were identified, which yielded more than 600 PC clusters and 8900 PCPs. Moreover, 520 PHs were obtained. Limitations & next steps: PC and PCP data structures capture structure–promiscuity relationships. Promiscuity assessment is also affected by data sparseness. Given the rapid growth of kinase inhibitor data, the relevance of PC/PCP/PH information for medicinal chemistry and chemical biology applications will further increase.