Cyclin D2 is a critical Achilles heel of multiple myeloma. To find drugs which target this gene we used a robotic screen of 6000 FDA approved drugs or natural compounds. We have identified a number of drugs in this screen which inhibit cyclin D2. We propose to confirm this finding in myeloma cell lines and patient samples. For the most promising drugs we will study mice to determine how to give the drug and to make sure the drug is effective in animals. We will also use a genomic strategy to gain a thorough understanding of their mechanism of action.