Estrogen sulfotransferase

Example 17 Bertozzi and associates in their studies on sulfotransferases have performed synthesis of a bisubstrate analogue designed to inhibit estrogen sulfotransferase [45]. Synthesis of this diphosphate depends on the coupling of two phosphates prepared by phosphoroamidite methodology. The synthesis utilizes differently protected 3 -phosphoadenosine-5 -phos-phate allowing selective functionalization of the 5 -phosphate with the sulfate acceptor mimic. 

M., Leary, J. A., Bertozzi, C. R. (2001) Discovery of estrogen sulfotransferase inhibitors from a purine library screen. J Med Chem 44, 2683-2686. 

Her C, Szumlanski C, Aksoy I, et al. Human jejunal estrogen sulfotransferase and dehydroepiandrosterone sulfotransferase. Immunochemical characterization of individual variation. Drug Metab Dispos 1996 24 1328-1335. 

Estrogen sulfotransferase green with consumed cofactor (PAP) and substrate (17(3-estradiol) in yellow uridylate kinase blue with consumed cofactor (ADP) and substrate analog (ADP) in red. 

The library was also tested with murine estrogen sulfotransferase (mEST). This screen afforded a purine-based inhibitor of mEST with nanomolar potency that displayed weak activity against several CDKs and selectivity for mEST when tested with representative members of the carbohydrate sulfotransferase family [63], Finally, a screen of the library against P-arylsulfotransferase-IV (P-AST-IV) led to the discovery of a potent, highly selective inhibitor (26, Scheme 14.7) of P-AST-IV (X = 96 nM). This compound was also screened against a variety of nucleotidebinding proteins (several kinases, sulfotransferases, and others) and proved to be selective [64],... 

Phenol sulfotransferases estrogen sulfotransferase Cytosol S9 hepatocytes... 

Kester MHA, Bulduk S, Tibboel D, et al. 2000. Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites A novel pathway explaining the estrogenic activity of PCBs. Endocrinology 141(5) 1897-1900. 

Lewis, A.)., Walle, U.K., King, R.S., Kadlubar, F.F., Falany, C.N., and Walle, T. (1998) Bioadivation of the cooked food mutagen N-hydroxy-2-amino-l-methyl-6-phenylimidazo[4,5-i>] pyridine by estrogen sulfotransferase in cultured human mammary epithelial cells. Carcinogenesis, 19, 2049-2053. 

Adams, J. B., Vrahimis, R., and Phillips, N. (1992) Regulation of estrogen sulfotransferase by estrogen in MCF-7 human mammary cancer cells. Breast Cancer Res. Treat. 22, 157-161. 

In addition to PXR and CAR, several other nuclear receptors, such as vitamin D receptor (VDR), hepatocyte nuclear factor 4a (HNF4a), peroxisome proliferator-activated receptors (PPARs), and farnesoid X receptor (FXR), have also been implicated in the regulation of xenobiotic enzymes and transporters [9-12], More recently, results from our lab have shown that the liver X receptor (LXR), a previously known sterol sensor, can also regulate the expression of phase II SULTs, such as the bile acid detoxifying hydroxysteroid sulfotransferase Sult2a9/2al [13] and the estrogen sulfotransferase (Est/Sultlel) [14],... 

Retinoic acid inhibits estrogen sulfotransferase, glutamate dehyrogenase, metaplasia shows antitumor activity. (The sufflx metaplasia means develc ment.)... 

Nakamura Y, Miki Y, Suzuki T, Nakata T, Darnel AD, Moriya T, Tazawa C, Saito H, Ishibashi T, Takahashi S, Yamada S, Sasano H.Steroid sulfatase and estrogen sulfotransferase in the atherosclerotic human aorta. Am J Pathol 2003 163 1329-1339. 

Y. Kakuta, E. V. Petrotchenko, L. C. Pedersen, M. Negishi, The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis. J. Biol Chem. 1998 273, 27325-30. 

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