Looking for Drugs in All the Wrong Places: Use of GCPII Inhibitors Outside the Brain.

Looking for Drugs in All the Wrong Places: Use of GCPII Inhibitors Outside the Brain. Neurochem Res. 2019 Nov 20;: Authors: Vornov JJ, Peters D, Nedelcovych M, Hollinger K, Rais R, Slusher BS Abstract In tribute to our friend and colleague Michael Robinson, we review his involvement in the identification, characterization and localization of the metallopeptidase glutamate carboxypeptidase II (GCPII), originally called NAALADase. While Mike was characterizing NAALADase in the brain, the protein was independently identified by other laboratories in human prostate where it was termed prostate specific membrane antigen (PSMA) and in the intestines where it was named Folate Hydrolase 1 (FOLH1). It was almost a decade to establish that NAALADase, PSMA, and FOLH1 are encoded by the same gene. The enzyme has emerged as a therapeutic target outside of the brain, with the most notable progress made in the treatment of prostate cancer and inflammatory bowel disease (IBD). PSMA-PET imaging with high affinity ligands is proving useful for the clinical diagnosis and staging of prostate cancer. A molecular radiotherapy based on similar ligands is in trials for metastatic castration-resistant prostate cancer. New PSMA inhibitor prodrugs that preferentially block kidney and salivary gland versus prostate tumor enzyme may improve the clinical safety of this radiotherapy. The wide clinical use of PSMA-PET imaging in prostate cancer has coincidentally l...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research