Raloxifene tissue-selectivity

Somjen D, Waisman A, Kaye AM (1996) Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo. J Steroid Biochem Mol Biol 59(5-6) 389-396... 

There also exist a class of ligands referred to as SERMs (selective estrogen receptor modulators) that display tissue-selective pharmacology [13]. Raloxifene and tamoxifen are two clinically used SERMs for which structures are available. Crystal structures of the estrogen receptor bound to different ligands (estradiol, tamoxifen, or raloxifene) reveal that ligands of different sizes and shapes induce a spectrum of receptor conformational states. These states can be interpreted by the cellular complexion of co-regulators and the environment of the local promoter of... 

SELECTIVE ESTROGEN RECEPTOR MODULATORS AND ANTIESTROGENS SERMs TAMOXIFEN, RALOXIFENE, AND TOREMIFENE Selective ER modulators, or SERMs, exert tissue-selective actions. Their pharmacological goal is to produce beneficial estrogenic actions in certain tissues (e.g., bone, brain, and Uver) but antagonist activity in others... 

A relevant finding of this study was the selective action of raloxifene on leiomyoma tissue highlighted by a significant increase in the difference be-... 

The potency of zebularine is about 10-fold lower than for the azacytosines [73]. Zebularine also inhibits cytidine deaminase [75] which is involved in nucleoside catabolism and deactivates also for example azacitidine and its desoxy analog [76]. Thus, it increases the concentrations of nucleoside triphosphates for incorporation into DNA, the efficacy of DNA methylation and ultimately the anticancer activity of for example azacitidine [77, 78[. Zebularine is metabolized by aldehyde oxidase and ithasbeen shovm that its activity can be increases if an inhibitor of that enzyme, for example raloxifene is given in combination [79]. One big question about all epigenetic drugs is the origin of the observed selectivity towards cancer cells. For zebularine, it has been shown that much less activation towards triphosphate metabolites that can be incorporated into DNA occurs in normal muscle tissue as compared to cancer tissue [80]. 

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