Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 64, Issue 8, Pages 4532-4552Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c01935
Keywords
-
Categories
Funding
- RFBR [2033-70089, 18-2908060]
- Ministry of Education and Science of the Russian Federation [03.G25.31.0219]
- Russian Science Foundation (RSF) [17-74-30012, 18-75-10008, 19-14-00115]
- Ministry of Education and Science of the Russian Federation in the Program of NUST MISIS [211]
- IBG RAS Ufa
- Russian Science Foundation [18-75-10008, 19-14-00115] Funding Source: Russian Science Foundation
Ask authors/readers for more resources
PSMA, which is overexpressed in prostate cancer cells, is a suitable target for specific delivery of antitumor drugs and diagnostic agents. The novel PSMA ligands designed exhibit strong inhibition on PSMA activity, with conjugates showing high affinity to PSMA-expressing tumor cells in vitro. In vivo biodistribution of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand in xenografts demonstrates good visualization of PSMA-expressing tumors, with no explicit toxicity observed up to 87.9 mg/kg.
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.9 mg/kg.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available