Androgen receptor structure

Nuclear Receptors as Drug Targets. Edited by Eckhard Ottow and Hilmar Weinmann Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31872-8 

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Roy AK, Tyagi RK, Song CS, et al. Androgen receptor structural domains and functional dynamics after ligand-receptor interaction. Ann N Y Acad Sci. 2001 949 44-57. 

Hirawat S, Budman DR, Kreis W. The androgen receptor structure, mutations, and antiandrogens. Cancer Invest. 2003 21 400M-17. 

Sex Steroid Receptors Androgen Receptor, Estrogen Receptors, Progesterone Receptor. Figure 1 Schematic structures of AR, ERa, ER(3, and PR. 

Flutamide, an androgen receptor antagonist possessing a different chemical structure, lacks progestin activity. 

Structural modifications of bicalutamide led to the discovery of the first generation of selective androgen receptor modulators (SARMs). These compounds not only bind to the AR with an affinity in the nanomolar range, but they also show tissue selectivity in animal models [206]. 

Waller CL. Juma BW, Gray JE Jr, Kelce WE (1996) Three-dimensional quantitative structure activity relationships for androgen receptor ligands. Toxicol Appl Pharmacol, 137 219-227. 

By considering the SARs observed in bioassays with knowledge of the crystal structure of receptor-androgen receptor interactions, Fang et al. [30] were able to make statements about the chemical structures most likely to be associated with binding to the AR. These are summarized in Table 18.3. 

Although detailed structural as well as mechanistic knowledge of an enzyme is desirable, it is by no means necessary in order to design a suicide substrate. This has been shown by Myers and Widlanski (1993) who have designed a simple inhibitor of human prostatic acid phosphatase (PAP), an enzyme that is believed to be involved in the regulation of androgen receptor activity in prostate cells. Since the enzyme shows a preference for hydrolysis of aryl phosphates, the 4-(fluoromethyl)-phenyl phosphate (FMPP) was prepared as a substrate that would, on hydrolysis by the... 

Soderholm, A.A., Lehtovuori, P.T., Nyro-nen, T. H. Three-dimensional Structure-Activity Relationships of Nonsteroidal Ligands in Complex with Androgen Receptor Ligand-binding Domain. J. Med. Chem. 2005, 48, 917-925. 

Chang CS, Kokontis J, Liao ST. Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors. Proc Natl Acad Sci USA 1988 85(19) 7211-7215. 

Gao W, Bohl CE, Dalton JT (2005) Chemistry and structural biology of androgen receptor. Chem Rev 105 3352-3370... 

Flutamide and bicalutamide are structurally different androgen receptor antagonists lacking progestin activity. 

Androgen receptor aberrations in structure or content may modify androgen action and in the prostate may lead to an increase in cancer. It is proposed that a disequilibrium in the CAG repeat lengths in the transactivation domain of the AR gene may be involved in the development of prostate cancer (S21). Other aberrations which can be involved in the progression of tumors from an... 

M31. Mulder, E., van Loon, D., de Boer, W., Schuurmans, A. L., Bolt., J., et al., Mechanism of androgen action recent observations on the domain structure of androgen receptors and the induction of EGF-receptors by androgens in prostate tumor cells. J. Steroid Biochem. 32,151—156 (1989). 

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