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Objective.Searching for more potent and less toxic HMBA related agents. Methods.Human erythroleukemia cell K562,murine erythroleukemia cell (MEL) and its sub line MEL DS19 were used as target cells to select a cell line which is the most sensitive to HMBA,then analyzed the activity of inducing differentiation of two new designed HMBA derivatives:HMBPA [hexamethylenebi (3 pyridin) amide] and Co HDTA (ethylenediaminetetra acetic acid cobalt) using cell biology,cytochemical and molecular biology techniques. Results.We found that the MEL DS19 cells were most sensitive to HMBA (benzidine positive,B+ ～76% ).Co HDTA can inhibit the growth of MEL DS19,but induces differentiation just in a small population (B+ 2% ～4.5% ).Between 0.02～5μ mol/L,HMBPA induces 3% ～8% cells committed to differentiation with little inhibition of cell proliferation.1μ mol/L HMBPA and 2mmol/L HMBA together,can obviously increase the percentage of differentiated cell (B+ ～72% ),inhibit DNA synthesis and accelerate β globin transcription. Conclusion.The new HMBA derivatives may provide potential cancer differentiation inducers.