An effective treatment of myeloid leukemias would rely on inducing myeloid cells to undergo differentiation. It has been demonstrated that inhibition of IMPDH with mycophenolic acid or tiazofurin resulted in inhibition of cell growth as well as induction of differentiation. We synthesized a number of bis(phosphonate) analogues of tiazofurin-, benzamide- , and mycophenolic-adenine dinucleotide which were found to be cytotoxic as well as effective inducers of cell differentiation.
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ACKNOWLEDGMENT The authors thanks Dr. Takashi Tsuji of Aijnomoto Co., Inc., Japan for a gift of mycophenolic acid. We also thank Dr. Koyichi A. Watanabe of Codon Pharmaceuticals, Inc., for his continued interest. This work was supported by NIH grant lR43GM54503-01A2