Androgen receptor affinity

Table 1 Evaluation of selected experimental agents as selective androgen receptor modulators. Entry 16 had a moderate androgen receptor affinity while entry 17 displayed a very high propensity as an androgen selective receptor binding agent. H NMR data supplied by author...

Campbell, P.M., Pottinger, T.G., and Sumpter, J.P. (1994). Changes in the affinity of estrogen and androgen receptors accompany changes in receptor abundance in Brown and Rainbow Trout. General and Comparative Endocrinology 94, 329-340. 

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]. 

Dihydrotestosterone is the preferred (high affinity) ligand for the androgen receptor and is formed by reduction of testosterone catalyzed by the enzyme steroid 50C-reductase. 

Conversion of testosterone to 5ar-dihydrotestosterone (5a-DHT). Receptor-binding studies indicate that 5a-DHT has a higher affinity for the androgen receptor than testosterone does. 

Nandrolones possess a very high affinity for androgen receptor-sites and bind more effectively than testosterone. This results in a significant increase in receptor-site binding time and greater activity. 

In clinical research, Metribolone is used to determine receptor-site affinity / displacement. Let me explain that. Metribolone is a very powerful androgen receptor-site stimulator and antagonist. I doubt there is any AAS more powerful. Since it binds so strongly to the receptor-site, researchers use the drug to see if other drugs can dislocate it, or for comparison. Not even Deca can kick it out of receptor-sites ... 

W. J. Computational Models for Predicting the Binding Affinities of Ligands for the Wild-type Androgen Receptor and a Mutated Variant Associated with Human Prostate Cancer. Chem. Res. Toxicd. 

Veldscholte J, Berrevoets CA, Brinkmann AO, Grootegoed JA, Mulder E. Anti-androgens and the mutated androgen receptor of LNCaP cells differential effects on binding affinity, heat-shock protein interaction, and transcription activation. Biochemistry 1992 31 (8) 2393—2399. 

Fig. 3. Specificity determined by ligand specificity of receptor. Oestradiol receptor has higher affinity for oestradiol (E2) than oestrone (E,) androgens (A) such as testosterone have very low affinity whilst progestins (P) and glucocorticoids (G) are inactive. Androgen receptor has less precise specificity recognising both P and G albeit with less affinity than androgens.

Androgen receptor binding affinities were determined using competitive binding assays described by Kirkovsky (1) and summarized in Table 1. 

Steroid Receptors. Steroid receptors such as estrogen, progesterone, and androgen receptors are overexpressed in breast, ovarian, and prostate cancers. Estrogen and progesterone receptors are present in about 65% of human breast cancers. The presence or absence of these receptors in cases of breast carcinoma assists the determination of the therapeutic strategy (hormonal or chemical) that is likely to be effective. The successful Tc complex must cross the membrane lipid bilayer of the cell, and thus, the size and lipophilicity of the complex must be balanced with receptorbinding affinity. 

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