Department of Pharmacology and Molecular Science, The Johns Hopkins University School of Medicine, Baltimore, MD 2131, USA.
Biol Chem. 2010 Apr;391(4):333-43. doi: 10.1515/BC.2010.044.
The role of prostate-specific antigen (PSA) or kallikrein-related peptidase 3 (KLK3) as a biomarker for prostate cancer is well known; however, the precise physiological role of it's serine protease activity in prostate cancer remains a mystery. PSA is produced at high levels by both androgen-dependent and -independent prostate cancers. Studies have documented high levels of active PSA in the milieu surrounding osseous and soft tissue metastases. This evidence, coupled with growing experimental evidence, suggests that PSA plays an important role in the pathobiology of prostate cancer. These observations support the development of PSA-selective inhibitors as useful tools for the targeted treatment and imaging of prostate cancer. Here, we review the research that has been conducted to date on developing selective inhibitors for PSA. The different approaches used to determine PSA substrate specificity and for creating inhibitors are discussed. In addition, the unique active site characteristics of PSA and how these motifs aided our research in developing PSA targeted agents are highlighted.
前列腺特异性抗原（PSA）或激肽释放酶相关肽 3（KLK3）作为前列腺癌的生物标志物的作用是众所周知的；然而，其丝氨酸蛋白酶活性在前列腺癌中的精确生理作用仍是一个谜。PSA 由雄激素依赖性和非依赖性前列腺癌大量产生。研究记录了骨和软组织转移周围环境中活性 PSA 的高水平。这一证据，加上不断增加的实验证据，表明 PSA 在前列腺癌的病理生物学中发挥着重要作用。这些观察结果支持开发 PSA 选择性抑制剂作为前列腺癌靶向治疗和成像的有用工具。在这里，我们回顾了迄今为止为开发 PSA 选择性抑制剂所进行的研究。讨论了用于确定 PSA 底物特异性和创建抑制剂的不同方法。此外，还突出了 PSA 独特的活性位点特征以及这些基序如何帮助我们研究开发 PSA 靶向药物。
