The prior MCA PAB funding enabled us to establish various biochemical and cell-based assays for screening and validation and to conduct high throughput screening and extensive post-screening validation in collaboration with the University of Kansas High Throughput Screening Laboratory (KU-HTSL). The prior research also highlighted the need to redesign the screening system to streamline the drug development process and widen the target range. The various assays that we established and in-depth scientific knowledge and insights we obtained in the prior research will help us accelerate the drug development process in the proposed research. We will continue to expand productive collaboration with KU core facilities to discover novel anticancer drugs. We are optimizing a new quadruple screening to discover inhibitors of both SH2 and SH3 domains of Crk and CrkL. The newly developed inhibitors will be used to advance studies of cancer and other human diseases in which Crk and CrkL play essential roles.