Background: Prostate cancer is one of the most common cancers worldwide, with
approximately 1.1 million cases diagnosed annually. The rapid development of molecular imaging
has facilitated greater structural understanding, which can help formulate novel combinations
of therapeutic regimens and more accurate diagnosis, avoiding unnecessary prostate biopsies.
This accumulated knowledge also provides a greater understanding of the aggressive
stages of the disease and tumor recurrence. Recently, much progress has been made on developing
peptidomimetic-based inhibitors as promising candidates to effectively bind to the prostate-
specific membrane antigen (PSMA), which is expressed by prostate cancer cells.
Objective: In this review, recent advances covering small-molecule and peptide-based
PSMA inhibitors will be extensively reviewed, providing a base for the rational design of
future PSMA inhibitors.
Method: Herein, the literature on selected PSMA inhibitors that have been developed from
1996 to 2020 were reviewed, emphasizing recent synthetic advances and chemical strategies
whilst highlighting therapeutic potential and drawbacks of each inhibitor.
Results: Synthesized inhibitors presented in this review demonstrate the clinical application
of certain PSMA inhibitors, exhibited in vitro and in vivo.
Conclusion: This review highlights the clinical potential of PSMA inhibitors, analyzing the
advantages and setbacks of the chemical synthetic methodologies utilized, setting precedence
for the discovery of novel PSMA inhibitors for future clinical applications.