The proteasome had been validated as an efficacious target for the treatment of cancer since the successful launch of bortezomib in 2003.The drug was approved to treat multiple myeloma and mantle cell lymphoma.Nowadays many structurally diverse proteasome inhibitors had been discovered,two of which are being tested in clinical trials.Recently clinical results pointed out that bortezomib showed some side-effects and toxicities,such nausea,omitting and serious peripheral nervous toxicity.Discovery of high selective and specific proteasome inhibitors may avoid the above side-effects.Some dipeptidyl boronic acid proteasome inhibitors constructed from hybrid amino acids-α and β amino acids were synthesized and biologically evaluated.The results displayed three leads showed the same active as bortezomib and less toxic.