We have started with the observation that DMSO is able to induce erythroleukemia cells to differentiate into normal erythrocytes, and developed this into a group of potent molecules that accomplish a number of important goals in cancer therapy with a wide range of cancer types. 1) The cancer cells cease growth. 2) They can differentiate into normal non-cancerous cells. 3) In some cases they undergo apoptosis, programmed cell death. The compounds do not show significant toxicity, are orally active, and the lead compound has been approved for human use by the U.S. FDA in October 2006, having successfully emerged from clinical trials with flying colors. Ours is the first member of this new class of drugs to be approved, histone deacetylase inhibitors, and it is now being widely studied against many cancers, and other diseases.

The intellectual path that led to the potent compounds will be described, and the evidence on their mode of action and the results of animal and human trials. The importance of only medium strength of binding to the receptor protein in this series will be discussed. The kinetic principles involved may be applicable to many other medicinal series.

Paul A. Marks, Ronald Breslow, �Dimethylsulphoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug,� Nature Biotech. 2007, 25, 84-90.

M. Tanaka, J. Levy, M. Terada, R. Breslow, R.A. Rifkind, P.A. Marks, "Induction of Erythroid Differentiation in Murine Virus Infected Erythroleukemia Cells by Highly Polar Compounds", Proc. Nat. Acad. Sci. USA, 72, 1003-1006 (1975).