K-7174 is a novel orally active, potent proteasome inhibitor. K-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases. K-7174 kills bortezomib-resistant myeloma cells carrying a β5-subunit mutation in vivo and primary cells from a patient resistant to bortezomib. K-7174 is also a GATA-specific inhibitor, which may have potential application in treating anemia of chronic disease.