Receptor androgen, binding affinity

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. 

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. 

B10. Brass, A. L., Barnard, J., Patai, B. L., Salvi, D., and Rukstalis, D. B., Androgen upregulates epidermal growth factor receptor expression and binding affinity in PC3 cell lines expressing the human androgen source receptor. Cancer Res. 55, 3197-3203 (1995). 

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

Table 7. Chemical structure, molecular formula, molecular mass, relative binding affinity (RBA) to the androgen receptor (AR), n-octanol/water partition coefficient (log Kqw)> and bioconcentration factors on a wet weight basis (BCF ) and on a lipid basis (BCFl) of Steroidal Androgens and Nonsteroidal Chemicals with Antiandrogenic Activity... 

RBA Relative binding affinity to the androgen receptor in comparison to 5a-dihydrotestosterone (DHT). The RBA values were calculated from Ref. [125b, c, d,jj. 

In another study [85], calculated BE values on a data set of 25 steroidal and nonsteroidal compounds for the rat androgen receptor (rAR) were plotted against the corresponding observed binding affinity (Kt). A strong correlation between the BE-predicted and experimental pK was found (R2 = 0.85) (Figure 6.16) [85], The BE values also reflected the observed loss in ligand specificity... 

Ai N, DeLisle RK, Yu S, Welsh WJ. Computational models for predicting binding affinities of ligands for the wild-type androgen receptor and a mutated variant associated with prostate cancer. Chem Res Toxicol 2003 16 1652-60. 

Serafimova R, Walker J, Mekenyan O. Androgen receptor binding affinity of pesticide active formulation ingredients QSAR evaluation by COREPA method. SAR QSAR Environ Res 2002 13 127-34. 

FIGURE 20.38 Structure and binding affinity to androgen receptor of non-steroidal SARMs. ... 

Change in sensitivity (or T level) or 4 binding affinity of target enzymes or receptors Etoposide, methotrexate, vinca alkaloids, estrogen and androgen receptors... 

He, Y., Yin, D., Perera, M., Kirkovsky, L., Stourman, N., Li, W., Dalton, J.T. and Miller, D.D. (2002) Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor. European Journal of Medicinal Chemistry, 37, 619-634. 

Pereira de Jesus-Tran, K., Cote, P.L., Cantin, L., Blanchet, J., Labrie, F. and Breton, R. (2006) Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity. Protein Science A Publication of the Protein Society, 15, 987-999. 

He Y, Yin D, Perera M, et al. Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor. Eur J Med Chem 2002 37 619-634. 

Figure 3. Compounds with a high binding affinity to the androgen receptor.

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