Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutic agents that induce tumor cell cytostasis, differentiation and apoptosis in various hematologic and solid malignancies.They may exert their anti-tumor activity through chromatin remodeling and gene expression modulation that affect cell cycle and survival pathways.In our HDAC program, we have designed and synthesized a series of benzimidazole based hydroxamic acids as HDAC inhibitors.SAR of substituents on the benzimidazole ring were explored.Within this series, selected compounds were evaluated in animal models for anti-tumor activity.These compounds produced significant tumor growth inhibition and tumor growth delay in HCT 116 bearing nude mice xenograft model.Further optimization of the lead compound produced SB939 with superior ADME attributes.The superior pharmacokinetics of SB939 also correlated well with the excellent anti-tumor activity observed in the in vivo xenograft model.SB939 was advanced into preclinical studies and IND was filed in 2006.It is currently in clinical trials.