Since CREB is constitutively overexpressed and hyperphosphorylated in human lung cancer tissues and cells and considered as a critical transcription factor in cancer pathogenesis [9–12], we identified several small molecule inhibitors of the CREB-CBP transcription factor/co-activator that target the binding domain KIX of CBP and prevent the formation of a complex with the KID domain of CREB. The gene discussed is CREB1; the disease is cancer.