Protein kinases represent an important target class for drug discovery because of their role in signaling pathways involved in disease areas such as oncology and immunology. A key element of many ATP-competitive kinase inhibitors is their hinge-binding motif. Here, we describe Kinase Crystal Miner (KCM)-a new approach developed at Boehringer Ingelheim (BI) that harvests the existing crystallographic information on kinase-inhibitor co-crystal structures from internal and external databases. About 1000 unique three-dimensional kinase inhibitor hinge binding motifs have been extracted from structures covering more than 180 different protein kinases. These hinge binding motifs along with their attachment vectors have been combined in the KCM for the purpose of scaffold hopping, kinase screening deck design, and interactive structure-based design. Prospective scaffold hopping using the KCM identified two potent and selective Bruton tyrosine kinase (BTK) inhibitors with hinge binding fragments novel to BTK.