Identification of new antiresorptives by disrupting subunit-subunit interactions unique for the a3-containing V-ATPases in osteoclasts. (a) A binding interaction between a3 and B2 was identified, and a high throughput screen was developed to identify small molecules that blocked the interaction. Such molecules would be expected to block V-ATPase assembly. (b) A binding interaction between a3 and d2 was detected and small molecules were sought to block this interaction. In this case, exclusion of d2 from an otherwise assembled pump might be expected. Mice in which d2 was knocked out suggested that this might both disrupt osteoclast resorption and also lead to stimulation of bone formation by osteoblasts.