CPP-1X (Eflornithine HCL [the monohydrochloride monohydrate of 2-(difluoromethyl) ornithine or DFMO] is a potent, enzyme-activated, irreversible inhibitor of the enzyme ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines.
Polyamines play critical roles in differentiation and proliferation of mammalian cells. Polyamines are also essential for neoplastic transformation, making inhibition of ODC activity an attractive target for cancer chemoprevention.
Sulindac and its metabolites function through their effects on cyclooxygenases and prostaglandin metabolism, but also on non-cyclooxygenase mechanisms. Sulindac induces the expression of the spermidine/spermine N-acetyltransferase SAT1, a polyamine catabolic gene product implicated in polyamine export via the cyclooxygenase-independent transcriptional activation of SAT1 by a peroxisomal proliferator-activated receptor gamma. This stimulates polyamine export and catabolism. Hence the combination of CPP-1X/sul inhibits the de novo generation of polyamines thru ODC inhibition and increasing the export and catabolism of polyamines with sulindac.