Phosphoramidate derivatives of hydroxysteroids as inhibitors of prostate-specific membrane antigen |
| |
Authors: | Wu Lisa Y Do Jacinda C Kazak Marat Page Helen Toriyabe Yoko Anderson Marc O Berkman Clifford E |
| |
Institution: | Department of Chemistry, Washington State University, Pullman, WA 99164-4630, USA. |
| |
Abstract: | Prostate-specific membrane antigen (PSMA) is a membrane-bound cell surface peptidase which is over-expressed in prostate cancer cells. The enzymatic activities of PSMA are understood but the role of the enzyme in prostate cancer remains conjectural. We previously confirmed the existence of a hydrophobic binding site remote from the enzyme's catalytic center. To explore the specificity and accommodation of this binding site, we prepared a series of six glutamate-containing phosphoramidate derivatives of various hydroxysteroids (1a-1f). The inhibitory potencies of the individual compounds of the series were comparable to a simple phenylalkyl analog (8), and in all cases IC50 values were sub-micromolar. Molecular docking was used to develop a binding model for these inhibitors and to understand their relative inhibitory potencies against PSMA. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|