Inhibitors of prostate-specific membrane antigen in the diagnosis and therapy of metastatic prostate cancer - a review of patent literature.
INTRODUCTION
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II, is a potential target protein for imaging and treatment of patients with prostate cancer because of its overexpression during metastasis. Various PSMA-targeted imaging and therapeutic probes have been designed and synthesized based on the Lys-urea-Glu motif. Structural modifications have been made exclusively in the linker region, while maintaining the Lys-urea-Glu structure that interacts with S1 and S1' pockets.


AREA COVERED
This review includes WIPO-listed patents (from January 2017 to June 2020) reporting PSMA-targeted probes based on the Lys-urea-Glu or Glu-urea-Glu structure.


EXPERT OPINION
: PSMA-targeted imaging agents labeled with radionuclides such as fluorine-18, copper-64, gallium-68, and technetium-99m have been successfully translated into clinical phase for the early diagnosis of metastatic prostate cancer. Recently, PSMA-targeted therapeutic agents labeled with iodine-131, lutetium-177, astatine-211, and lead-212 have also been developed with notable progress. Most PSMA-targeted agents are based on the Lys-urea-Glu or Glu-urea-Glu structure, demonstrate strong PSMA-binding affinity in nanomolar range, and achieve diverse structural modifications in the non-pharmacophore pocket. By exploiting the S1 accessory pocket or the tunnel region of the PSMA active site, the in vivo efficacy and pharmacokinetic profiles of the PMSA-targeted agents can be effectively modulated.
['Ha|Hyunsoo|H|https://orcid.org/0000-0002-9438-1179', 'Kwon|Hongmok|H|https://orcid.org/0000-0001-6858-2674', 'Lim|Taehyeong|T|https://orcid.org/0000-0001-9406-6577', 'Jang|Jaebong|J|https://orcid.org/0000-0002-7962-3395', 'Park|Song-Kyu|SK|https://orcid.org/0000-0002-2858-2300', 'Byun|Youngjoo|Y|https://orcid.org/0000-0002-0297-7734']
D000818:Animals D000954:Antigens, Surface D000970:Antineoplastic Agents D015195:Drug Design D043425:Glutamate Carboxypeptidase II D006801:Humans D008297:Male D058990:Molecular Targeted Therapy D009362:Neoplasm Metastasis D010330:Patents as Topic D011471:Prostatic Neoplasms D013329:Structure-Activity Relationship
metastatic prostate cancer Prostate-specific membrane antigen (PSMA) Lys-urea-Glu radionuclides imaging probes