2. Academic Validation
  3. Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them

Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them

  • J Med Chem. 2021 Apr 22;64(8):4532-4552. doi: 10.1021/acs.jmedchem.0c01935.
Aleksei E Machulkin 1,  Radik R Shafikov 1 2,  Anastasia A Uspenskaya 1,  Stanislav A Petrov 1,  Anton P Ber 1,  Dmitry A Skvortsov 1 3,  Ekaterina A Nimenko 1,  Nikolay U Zyk 1,  Galina B Smirnova 4,  Vadim S Pokrovsky 4 5,  Maxim A Abakumov 6,  Irina V Saltykova 1,  Rauf T Akhmirov 7,  Anastasiia S Garanina 6,  Vladimir I Polshakov 8,  Oleg Y Saveliev 8,  Yan A Ivanenkov 1 9 6 10 11,  Anastasiya V Aladinskaya 9,  Alexander V Finko 1,  Emil U Yamansarov 1,  Olga O Krasnovskaya 1 6,  Alexander S Erofeev 1 6,  Petr V Gorelkin 1 6,  Olga A Dontsova 1 2,  Elena K Beloglazkina 1,  Nikolay V Zyk 1,  Elena S Khazanova 12,  Alexander G Majouga 1 6 7
Affiliations

Affiliations

  • 1 Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.
  • 2 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, Moscow 117997, Russian Federation.
  • 3 Faculty of Biology and Biotechnologies, Higher School of Economics, Myasnitskaya 13, Moscow 101000, Russia.
  • 4 N.N. Blokhin Cancer Research Center, 24 Kashirskoye sh., Moscow 115478 , Russia.
  • 5 RUDN University, Miklukho-Maklaya str. 6, Moscow 117198, Russian Federation.
  • 6 National University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian Federation.
  • 7 Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian Federation.
  • 8 Center for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow 119991, Russian Federation.
  • 9 Moscow Institute of Physics and Technology (State University), 9 Institutskiy Lane, Dolgoprudny City, Moscow Region 141700, Russian Federation.
  • 10 The Federal State Unitary Enterprise Dukhov Automatics Research Institute, Moscow 127055, Russia.
  • 11 Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, Ufa 450054, Russian Federation.
  • 12 Izvarino Pharma LLC, v. Vnukovskoe, Vnukovskoe sh., 5th km., Building 1, Moscow 108817, Russian Federation.
PMID: 33822606 DOI: 10.1021/acs.jmedchem.0c01935
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-160893
    99.43%, PSMA Ligand