Over-expression of cyclin D2 occurs frequently in myeloma and contributes to the proliferation of the malignant plasma cells. Cyclin D2 expression is regulated by several transcription factors including c-maf that is dysregulated in ~50% of cases of myeloma. Therefore, small-molecules that inhibit cyclin D2 +- c-maf could be therapeutically useful for the treatment of myeloma. In our preliminary work, we have developed, validated, and automated a luciferase-based assay to identify inhibitors of cyclin D2 expression. We propose to use this assay to screen the Prestwick library and identify new drugs that inhibit cyclin D2 transactivation amd may be new anti-myeloma agents.