Medicinal Chemistry Research Program: Project Summary The Medicinal Chemistry Program (MC) in the Purdue University Center for Cancer Research (PCCR) drives the drug discovery effort of the Center by serving as the central component for basic research in cancer drug discovery and drug discovery methods. The Program consists of 23 members who integrate their expertise in novel synthetic strategies and advanced technologies with the other Research Programs in the Center, to advance translation of promising entities to the clinic. During the past four years, nine new cancer- focused faculty members were recruited to the MC Program. MC members are united by a focus on cancer drug discovery, and represent diverse disciplines that are drawn from seven academic departments and four colleges from across the Purdue campus. The MC Program has a strong publication record, producing 286 papers between 2010 and 2013 with 2% involving intra-programmatic collaborations, 19% representing inter- programmatic and 21% engaging inter-institutional partners; overall, 39% MC publications were a result of collaborative efforts with other cancer researchers. Combined, the MC membership has a current portfolio of over $1.7 million of total direct peer-reviewed, extramural support, with 44% of awards being cancer-focused grants funded by the NCI, NSF, ACS or DOD. The MC Program is structured around two Research Clusters. Research Cluster 1, Synthetic Medicinal Chemistry, and the cornerstone of the MC Program, reflects the strengths of the Center in medicinal chemistry. A distinguished group of senior and junior faculty develops and utilizes target-based medicinal chemistry approaches to drug discovery. The efforts of this group have led to the development of 13 agents that have been in Phase 0, Phase I, Phase II, or Phase III clinical trials in the last funding cycle. Ten other agents have progressed to preclinical development (in vivo studies). Research Cluster 2, Target Discovery and Translation, encompasses a focus on target discovery, in vitro and in cell molecular evaluation of potential anti-cancer therapeutic agents, and the development and use of in vivo models and methods for the analysis of potential anti-cancer drugs. Tools have been developed for high- throughput single cell screening as well as in cell sensing and identifying protein-protein interaction networks. There is a specific emphasis on comparative oncology including studies of dogs with naturally-occurring cancers that closely mimic the human condition. The canine models are being evaluated for their impact on the translation of therapeutic agents to humans. Over the past four years, many MC projects have spawned highly productive inter-programmatic collaborations involving members of the Cell Identity and Signaling (CIS), Chemical and Structural Biology (CSB), and Drug Delivery and Molecular Sensing (DDMS) Programs. The Program Leader and Co-Leader's efforts in cancer-focused faculty recruiting and mentoring, and organizing Program meetings and the PCCR-based Bladder Cancer Discovery Group, have enhanced the two Research Clusters and overall research progress of the MC Program.