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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist.

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.[1]


  1. Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist. Hait, W.N., Glazer, L., Kaiser, C., Cross, J., Kennedy, K.A. Mol. Pharmacol. (1987) [Pubmed]
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