Evolution of Peptide-Based Prostate-Specific Membrane Antigen (PSMA) Inhibitors: An Approach to Novel Prostate Cancer Therapeutics

Andrew       Siow; Renata       Kowalczyk; Margaret    A.    Brimble; Paul    W.R.    Harris
doi:10.2174/0929867327666201006153847
Abstract

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.
Keywords: PSMA inhibitors, tumor targeting, peptides, positron emission tomography (PET) imaging, PSMA inhibitors, prostate cancer.
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[1] 
Ghosh, A.; Heston, W.D.W. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J. Cell. Biochem.,  2004, 91(3), 528-539.
[http://dx.doi.org/10.1002/jcb.10661] [PMID: 14755683] 
[2] 
Haffner, M.C.; Laimer, J.; Chaux, A.; Schäfer, G.; Obrist, P.; Brunner, A.; Kronberger, I.E.; Laimer, K.; Gurel, B.; Koller, J.-B.; Seifarth, C.; Zelger, B.; Klocker, H.; Rasse, M.; Doppler, W.; Bander, N.H. High expression of prostate specific membrane antigen in the tumor-associated neo vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. Mod. Pathol.,  2012, 25(8), 1079-1085.
[http://dx.doi.org/10.1038/modpathol.2012.66] [PMID: 22460809] 
[3] 
Wu, J.; Han, D.; Shi, S.; Zhang, Q.; Zheng, G.; Wei, M.; Han, Y.; Li, G.; Yang, F.; Jiao, D.; Xie, P.; Zhang, L.; Yang, A-G.; Zhao, A.; Qin, W.; Wen, W. A novel fully human antibody targeting extracellular domain of PSMA inhibits tumor growth in prostate cancer. Mol. Cancer Ther.,  2019, 18(7), 1289-1301.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-1078] [PMID: 31048359] 
[4] 
Chang, S.S.; Reuter, V.E.; Heston, W.D.W.; Bander, N.H.; Grauer, L.S.; Gaudin, P.B. Five different anti-prostate specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res.,  1999, 59(13), 3192-3198.
[PMID: 10397265] 
[5] 
Huang, X.; Bennett, M.; Thorpe, P.E. Anti-tumor effects and lack of side effects in mice of an immunotoxin directed against human and mouse prostate-specific membrane antigen. Prostate,  2004, 61(1), 1-11.
[http://dx.doi.org/10.1002/pros.20074] [PMID: 15287089] 
[6] 
Banerjee, S.R.; Ngen, E.J.; Rotz, M.W.; Kakkad, S.; Lisok, A.; Pracitto, R.; Pullambhatla, M.; Chen, Z.; Shah, T.; Artemov, D.; Meade, T.J.; Bhujwalla, Z.M.; Pomper, M.G. Synthesis and evaluation of Gd(III)-based magnetic resonance contrast agents for molecular imaging of prostate specific membrane antigen. Angew. Chem. Int. Ed. Engl.,  2015, 54(37), 10778-10782.
[http://dx.doi.org/10.1002/anie.201503417] [PMID: 26212031] 
[7] 
Davis, M.I.; Bennett, M.J.; Thomas, L.M.; Bjorkman, P.J. Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. Proc. Natl. Acad. Sci.,  2017, 102(17), 5981-5986.
[http://dx.doi.org/10.1073/pnas.0502101102] [PMID: 15837926] 
[8] 
Pang, S.-T.; Lin, F.-W.; Chuang, C.-K.; Yang, H.-W. Co-delivery of docetaxel and P44/42 MAPK SiRNA using PSMA antibody-conjugated BSA-PEI layer-by-layer nanoparticles for prostate cancer target therapy. Macromol. Biosci.,  2017, 17(5), 1600421.
[http://dx.doi.org/10.1002/mabi.201600421] [PMID: 28128882] 
[9] 
Bandekar, A.; Zhu, C.; Jindal, R.; Bruchertseifer, F.; Morgenstern, A.; Sofou, S. Anti-prostate-specific membrane antigen liposomes loaded with 225Ac for potential targeted antivascular α-particle therapy of cancer. J. Nucl. Med.,  2014, 55(1), 107-114.
[http://dx.doi.org/10.2967/jnumed.113.125476] [PMID: 24337602] 
[10] 
Wong, P.; Li, L.; Chea, J.; Delgado, M.K.; Crow, D.; Poku, E.; Szpikowska, B.; Bowles, N.; Channappa, D.; Colcher, D.; Wong, J.Y.C.; Shively, J.E.; Yazaki, P.J. PET imaging of 64Cu-DOTA-scFv-anti-PSMA lipid nanoparticles (LNPs): enhanced tumor targeting over anti-PSMA scFv or untargeted LNPs. Nucl. Med. Biol.,  2017, 47, 62-68.
[http://dx.doi.org/10.1016/j.nucmedbio.2017.01.004] [PMID: 28126683] 
[11] 
Gilboa, E.; McNamara, J., II; Pastor, F. Use of oligonucleotide aptamer ligands to modulate the function of immune receptors. Clin. Cancer Res.,  2013, 19(5), 1054-1062.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2067] [PMID: 23460536] 
[12] 
Wang, X.; Huang, S.S.; Heston, W.D.W.; Guo, H.; Wang, B.-C.; Basilion, J.P. Development of targeted near-infrared imaging agents for prostate cancer. Mol. Cancer Ther.,  2014, 13(11), 2595-2606.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0422] [PMID: 25239933] 
[13] 
Ruggiero, A.; Holland, J.P.; Lewis, J.S.; Grimm, J. Cerenkov luminescence imaging of medical isotopes. J. Nucl. Med.,  2010, 51(7), 1123-1130.
[http://dx.doi.org/10.2967/jnumed.110.076521] [PMID: 20554722] 
[14] 
Jackson, P.F.; Cole, D.C.; Slusher, B.S.; Stetz, S.L.; Ross, L.E.; Donzanti, B.A.; Trainor, D.A. Design, synthesis, and biological activity of a potent inhibitor of the neuropeptidase N-acetylated α-linked acidic dipeptidase. J. Med. Chem.,  1996, 39(2), 619-622.
[http://dx.doi.org/10.1021/jm950801q] [PMID: 8558536] 
[15] 
Curatolo, A.; D Arcangelo, P.; Lino, A.; Brancati, A. Distribution of N-acetyl-aspartic and N-acetyl-aspartyl-glutamic acids in nervous tissue. J. Neurochem.,  1965, 12(4), 339-342.
[http://dx.doi.org/10.1111/j.1471-4159.1965.tb06771.x] [PMID: 14340686] 
[16] 
Son, S.-H.; Kwon, H.; Ahn, H.-H.; Nam, H.; Kim, K.; Nam, S.; Choi, D.; Ha, H.; Minn, I.; Byun, Y. Design and synthesis of a novel BODIPY-labeled PSMA inhibitor. Bioorg. Med. Chem. Lett.,  2020, 30(3), 126894.
[http://dx.doi.org/10.1016/j.bmcl.2019.126894] [PMID: 31874825] 
[17] 
Machulkin, A.E.; Ivanenkov, Y.A.; Aladinskaya, A.V.; Veselov, M.S.; Aladinskiy, V.A.; Beloglazkina, E.K.; Koteliansky, V.E.; Shakhbazyan, A.G.; Sandulenko, Y.B.; Majouga, A.G. Small-molecule PSMA ligands. Current state, SAR and perspectives. J. Drug Target.,  2016, 24(8), 679-693.
[http://dx.doi.org/10.3109/1061186X.2016.1154564] [PMID: 26887438] 
[18] 
Vitharana, D.; France, J.E.; Scarpetti, D.; Bonneville, G.W.; Majer, P.; Tsukamoto, T. Synthesis and biological evaluation of (R)- and (S)-2-(phosphonomethyl)pentanedioic acids as inhibitors of glutamate carboxypeptidase II. Tetrahedr. Asymm.,  2002, 13(15), 1609-1614.
[http://dx.doi.org/10.1016/S0957-4166(02)00412-3] 
[19] 
Jackson, P.F.; Tays, K.L.; Maclin, K.M.; Ko, Y.-S.; Li, W.; Vitharana, D.; Tsukamoto, T.; Stoermer, D.; Lu, X.-C.M.; Wozniak, K.; Slusher, B.S. Design and pharmacological activity of phosphinic acid based NAALADase inhibitors. J. Med. Chem.,  2001, 44(24), 4170-4175.
[http://dx.doi.org/10.1021/jm0001774] [PMID: 11708918] 
[20] 
Tsukamoto, T.; Flanary, J.M.; Rojas, C.; Slusher, B.S.; Valiaeva, N.; Coward, J.K. Phosphonate and phosphinate analogues of N-acylated γ-glutamylglutamate. potent inhibitors of glutamate carboxypeptidase II. Bioorg. Med. Chem. Lett.,  2002, 12(16), 2189-2192.
[http://dx.doi.org/10.1016/S0960-894X(02)00360-8] [PMID: 12127534] 
[21] 
Nan, F.; Bzdega, T.; Pshenichkin, S.; Wroblewski, J.T.; Wroblewska, B.; Neale, J.H.; Kozikowski, A.P. Dual function glutamate-related ligands: discovery of a novel, potent inhibitor of glutamate carboxypeptidase II possessing mGluR3 agonist activity. J. Med. Chem.,  2000, 43(5), 772-774.
[http://dx.doi.org/10.1021/jm9905559] [PMID: 10715144] 
[22] 
Tsukamoto, T.; Majer, P.; Vitharana, D.; Ni, C.; Hin, B.; Lu, X-C.M.; Thomas, A.G.; Wozniak, K.M.; Calvin, D.C.; Wu, Y.; Slusher, B.S.; Scarpetti, D.; Bonneville, G.W. Enantiospecificity of glutamate carboxypeptidase II inhibition. J. Med. Chem.,  2005, 48(7), 2319-2324.
[http://dx.doi.org/10.1021/jm049258g] [PMID: 15801825] 
[23] 
Synold, T.W.; Willits, E.M.; Barredo, J.C. Role of folylpolygutamate synthetase (FPGS) in antifolate chemotherapy; a biochemical and clinical update. Leuk. Lymphoma,  1996, 21(1-2), 9-15.
[http://dx.doi.org/10.3109/10428199609067573] [PMID: 8907263] 
[24] 
Barinka, C.; Hlouchova, K.; Rovenska, M.; Majer, P.; Dauter, M.; Hin, N.; Ko, Y.-S.; Tsukamoto, T.; Slusher, B.S.; Konvalinka, J.; Lubkowski, J. Structural basis of interactions between human glutamate carboxypeptidase II and its substrate analogs. J. Mol. Biol.,  2008, 376(5), 1438-1450.
[http://dx.doi.org/10.1016/j.jmb.2007.12.066] [PMID: 18234225] 
[25] 
Lu, H.; Ng, R.J.; Shieh, C.C.; Martinez, A.R.; Berkman, C.E. Inhibition of glutamate carboxypeptidase by phosphoryl and thiophosphoryl derivatives of glutamic and 2-hydroxyglutaric acid. Phosphorus Sulfur Silicon Relat. Elem.,  2003, 178(1), 17-32.
[http://dx.doi.org/10.1080/10426500307817] 
[26] 
Maung, J.; Mallari, J.P.; Girtsman, T.A.; Wu, L.Y.; Rowley, J.A.; Santiago, N.M.; Brunelle, A.N.; Berkman, C.E. Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates. Bioorg. Med. Chem.,  2004, 12(18), 4969-4979.
[http://dx.doi.org/10.1016/j.bmc.2004.06.031] [PMID: 15336276] 
[27] 
Ganguly, T.; Dannoon, S.; Hopkins, M.R.; Murphy, S.; Cahaya, H.; Blecha, J.E.; Jivan, S.; Drake, C.R.; Barinka, C.; Jones, E.F.; VanBrocklin, H.F.; Berkman, C.E.A. A high-affinity [(18)F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer. Nucl. Med. Biol.,  2015, 42(10), 780-787.
[http://dx.doi.org/10.1016/j.nucmedbio.2015.06.003] [PMID: 26169882] 
[28] 
Krise, J.P.; Stella, V.J. Prodrugs of phosphates, phosphonates, and phosphinates. Adv. Drug Deliv. Rev.,  1996, 19(2), 287-310.
[http://dx.doi.org/10.1016/0169-409X(95)00111-J] 
[29] 
Gehr, T.W.B.; Sica, D.A.; Grasela, D.M.; Duchin, K.L. The pharmacokinetics and pharmacodynamics of fosinopril in haemodialysis patients. Eur. J. Clin. Pharmacol.,  1993, 45(5), 431-436.
[http://dx.doi.org/10.1007/BF00315514] [PMID: 8112372] 
[30] 
Zhong, C.; Luo, Q.; Jiang, J. Blockade of N-acetylaspar-tylglutamate peptidases: a novel protective strategy for brain injuries and neurological disorders. Int. J. Neurosci.,  2014, 124(12), 867-873.
[http://dx.doi.org/10.3109/00207454.2014.890935] [PMID: 24494725] 
[31] 
Majer, P.; Jackson, P.F.; Delahanty, G.; Grella, B.S.; Ko, Y.-S.; Li, W.; Liu, Q.; Maclin, K.M.; Poláková, J.; Shaffer, K.A.; Stoermer, D.; Vitharana, D.; Wang, E.Y.; Zakrzewski, A.; Rojas, C.; Slusher, B.S.; Wozniak, K.M.; Burak, E.; Limsakun, T.; Tsukamoto, T. Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor. J. Med. Chem.,  2003, 46(10), 1989-1996.
[http://dx.doi.org/10.1021/jm020515w] [PMID: 12723961] 
[32] 
Dannoon, S.; Ganguly, T.; Cahaya, H.; Geruntho, J.J.; Galliher, M.S.; Beyer, S.K.; Choy, C.J.; Hopkins, M.R.; Regan, M.; Blecha, J.E.; Skultetyova, L.; Drake, C.R.; Jivan, S.; Barinka, C.; Jones, E.F.; Berkman, C.E.; VanBrocklin, H.F. Structure-activity relationship of (18)F-labeled phosphoramidate peptidomimetic prostate-specific membrane antigen (PSMA)-targeted inhibitor analogues for PET imaging of prostate cancer. J. Med. Chem.,  2016, 59(12), 5684-5694.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01850] [PMID: 27228467] 
[33] 
Choy, C.J.; Ling, X.; Geruntho, J.J.; Beyer, S.K.; Latoche, J.D.; Langton-Webster, B.; Anderson, C.J.; Berkman, C.E. 177Lu-labeled phosphoramidate-based PSMA inhibitors: the effect of an albumin binder on biodistribution and therapeutic efficacy in prostate tumor-bearing mice. Theranostics,  2017, 7(7), 1928-1939.
[http://dx.doi.org/10.7150/thno.18719] [PMID: 28638478] 
[34] 
Majer, P.; Hin, B.; Stoermer, D.; Adams, J.; Xu, W.; Duvall, B.R.; Delahanty, G.; Liu, Q.; Stathis, M.J.; Wozniak, K.M.; Slusher, B.S.; Tsukamoto, T. Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1′ side chain. J. Med. Chem.,  2006, 49(10), 2876-2885.
[http://dx.doi.org/10.1021/jm051019l] [PMID: 16686531] 
[35] 
Kozikowski, A.P.; Nan, F.; Conti, P.; Zhang, J.; Ramadan, E.; Bzdega, T.; Wroblewska, B.; Neale, J.H.; Pshenichkin, S.; Wroblewski, J.T. Design of remarkably simple, yet potent urea-based inhibitors of glutamate carboxypeptidase II (NAALADase). J. Med. Chem.,  2001, 44(3), 298-301.
[http://dx.doi.org/10.1021/jm000406m] [PMID: 11462970] 
[36] 
Barinka, C.; Byun, Y.; Dusich, C.L.; Banerjee, S.R.; Chen, Y.; Castanares, M.; Kozikowski, A.P.; Mease, R.C.; Pomper, M.G.; Lubkowski, J. Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization. J. Med. Chem.,  2008, 51(24), 7737-7743.
[http://dx.doi.org/10.1021/jm800765e] [PMID: 19053759] 
[37] 
Mlcochová, P.; Plechanovová, A.; Bařinka, C.; Mahadevan, D.; Saldanha, J.W.; Rulísek, L.; Konvalinka, J. Mapping of the active site of glutamate carboxypeptidase II by site-directed mutagenesis. FEBS J.,  2007, 274(18), 4731-4741.
[http://dx.doi.org/10.1111/j.1742-4658.2007.06021.x] [PMID: 17714508] 
[38] 
Mesters, J.R.; Barinka, C.; Li, W.; Tsukamoto, T.; Majer, P.; Slusher, B.S.; Konvalinka, J.; Hilgenfeld, R. Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer. EMBO J.,  2006, 25(6), 1375-1384.
[http://dx.doi.org/10.1038/sj.emboj.7600969] [PMID: 16467855] 
[39] 
Klusák, V.; Bařinka, C.; Plechanovová, A.; Mlcochová, P.; Konvalinka, J.; Rulísek, L.; Lubkowski, J. Reaction mechanism of glutamate carboxypeptidase II revealed by mutagenesis, X-ray crystallography, and computational methods. Biochemistry,  2009, 48(19), 4126-4138.
[http://dx.doi.org/10.1021/bi900220s] [PMID: 19301871] 
[40] 
Bařinka, C.; Rovenská, M.; Mlcochová, P.; Hlouchová, K.; Plechanovová, A.; Majer, P.; Tsukamoto, T.; Slusher, B.S.; Konvalinka, J.; Lubkowski, J. Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II. J. Med. Chem.,  2007, 50(14), 3267-3273.
[http://dx.doi.org/10.1021/jm070133w] [PMID: 17567119] 
[41] 
Plechanovová, A.; Byun, Y.; Alquicer, G.; Skultétyová, L.; Mlčochová, P.; Němcová, A.; Kim, H-J.; Navrátil, M.; Mease, R.; Lubkowski, J.; Pomper, M.; Konvalinka, J.; Rulíšek, L.; Bařinka, C. Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity. J. Med. Chem.,  2011, 54(21), 7535-7546.
[http://dx.doi.org/10.1021/jm200807m] [PMID: 21923190] 
[42] 
Choy, C.J.; Fulton, M.D.; Davis, A.L.; Hopkins, M.; Choi, J.K.; Anderson, M.O.; Berkman, C.E. Rationally designed sulfamides as glutamate carboxypeptidase II inhibitors. Chem. Biol. Drug Des.,  2013, 82(5), 612-619.
[http://dx.doi.org/10.1111/cbdd.12174] [PMID: 23773397] 
[43] 
Park, J.D.; Kim, D.H.; Kim, S.-J.; Woo, J.-R.; Ryu, S.E. Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition state analogue inhibitors for zinc proteases. J. Med. Chem.,  2002, 45(24), 5295-5302.
[http://dx.doi.org/10.1021/jm020258v] [PMID: 12431056] 
[44] 
Kozikowski, A.P.; Zhang, J.; Nan, F.; Petukhov, P.A.; Grajkowska, E.; Wroblewski, J.T.; Yamamoto, T.; Bzdega, T.; Wroblewska, B.; Neale, J.H. Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents. J. Med. Chem.,  2004, 47(7), 1729-1738.
[http://dx.doi.org/10.1021/jm0306226] [PMID: 15027864] 
[45] 
Chen, Y.; Foss, C.A.; Byun, Y.; Nimmagadda, S.; Pullambhatla, M.; Fox, J.J.; Castanares, M.; Lupold, S.E.; Babich, J.W.; Mease, R.C.; Pomper, M.G. Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer. J. Med. Chem.,  2008, 51(24), 7933-7943.
[http://dx.doi.org/10.1021/jm801055h] [PMID: 19053825] 
[46] 
Kim, K.; Kwon, H.; Barinka, C.; Motlova, L.; Nam, S.; Choi, D.; Ha, H.; Nam, H.; Son, S.-H.; Minn, I.; Pomper, M.G.; Yang, X.; Kutil, Z.; Byun, Y. Novel β- and γ-amino acid-derived inhibitors of prostate-specific membrane antigen. J. Med. Chem.,  2020, 63(6), 3261-3273.
[http://dx.doi.org/10.1021/acs.jmedchem.9b02022] [PMID: 32097010] 
[47] 
Banerjee, S.R.; Foss, C.A.; Castanares, M.; Mease, R.C.; Byun, Y.; Fox, J.J.; Hilton, J.; Lupold, S.E.; Kozikowski, A.P.; Pomper, M.G. Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J. Med. Chem.,  2008, 51(15), 4504-4517.
[http://dx.doi.org/10.1021/jm800111u] [PMID: 18637669] 
[48] 
Maresca, K.P.; Hillier, S.M.; Femia, F.J.; Keith, D.; Barone, C.; Joyal, J.L.; Zimmerman, C.N.; Kozikowski, A.P.; Barrett, J.A.; Eckelman, W.C.; Babich, J.W. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J. Med. Chem.,  2009, 52(2), 347-357.
[http://dx.doi.org/10.1021/jm800994j] [PMID: 19111054] 
[49] 
Chandran, S.S.; Banerjee, S.R.; Mease, R.C.; Pomper, M.G.; Denmeade, S.R. Characterization of a targeted nanoparticle functionalized with a urea-based inhibitor of prostate-specific membrane antigen (PSMA). Cancer Biol. Ther.,  2008, 7(6), 974-982.
[http://dx.doi.org/10.4161/cbt.7.6.5968] [PMID: 18698158] 
[50] 
Banerjee, S.R.; Pullambhatla, M.; Byun, Y.; Nimmagadda, S.; Green, G.; Fox, J.J.; Horti, A.; Mease, R.C.; Pomper, M.G. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J. Med. Chem.,  2010, 53(14), 5333-5341.
[http://dx.doi.org/10.1021/jm100623e] [PMID: 20568777] 
[51] 
Fani, M.; André, J.P.; Maecke, H.R. 68Ga-PET: a powerful generator-based alternative to cyclotron-based PET radiopharmaceuticals. Contrast Media Mol. Imaging,  2008, 3(2), 67-77.
[http://dx.doi.org/10.1002/cmmi.232] [PMID: 18383558] 
[52] 
Kularatne, S.A.; Zhou, Z.; Yang, J.; Post, C.B.; Low, P.S. Design, synthesis, and preclinical evaluation of prostate-specific membrane antigen targeted (99m)Tc-radioimaging agents. Mol. Pharm.,  2009, 6(3), 790-800.
[http://dx.doi.org/10.1021/mp9000712] [PMID: 19361232] 
[53] 
Eder, M.; Schäfer, M.; Bauder-Wüst, U.; Hull, W.E.; Wängler, C.; Mier, W.; Haberkorn, U.; Eisenhut, M. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug. Chem.,  2012, 23(4), 688-697.
[http://dx.doi.org/10.1021/bc200279b] [PMID: 22369515] 
[54] 
Eder, M.; Wängler, B.; Knackmuss, S.; LeGall, F.; Little, M.; Haberkorn, U.; Mier, W.; Eisenhut, M. Tetrafluorophenolate of HBED-CC: a versatile conjugation agent for 68Ga-labeled small recombinant antibodies. Eur. J. Nucl. Med. Mol. Imaging,  2008, 35(10), 1878-1886.
[http://dx.doi.org/10.1007/s00259-008-0816-z] [PMID: 18509635] 
[55] 
Afshar-Oromieh, A.; Avtzi, E.; Giesel, F.L.; Holland-Letz, T.; Linhart, H.G.; Eder, M.; Eisenhut, M.; Boxler, S.; Hadaschik, B.A.; Kratochwil, C.; Weichert, W.; Kopka, K.; Debus, J.; Haberkorn, U. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur. J. Nucl. Med. Mol. Imaging,  2015, 42(2), 197-209.
[http://dx.doi.org/10.1007/s00259-014-2949-6] [PMID: 25411132] 
[56] 
Demirci, E.; Ocak, M.; Kabasakal, L.; Decristoforo, C.; Talat, Z.; Halaç, M.; Kanmaz, B. (68)Ga-PSMA PET/CT imaging of metastatic clear cell renal cell carcinoma. Eur. J. Nucl. Med. Mol. Imaging,  2014, 41(7), 1461-1462.
[http://dx.doi.org/10.1007/s00259-014-2766-y] [PMID: 24756358] 
[57] 
Gourni, E.; Canovas, C.; Goncalves, V.; Denat, F.; Meyer, P.T.; Maecke, H.R. (R)-NODAGA-PSMA: a versatile precursor for radiometal labeling and nuclear imaging of PSMA-positive tumors. PLoS One,  2015, 10(12), e0145755.
[http://dx.doi.org/10.1371/journal.pone.0145755] [PMID: 26700033] 
[58] 
Hoberück, S.; Wunderlich, G.; Michler, E.; Hölscher, T.; Walther, M.; Seppelt, D.; Platzek, I.; Zöphel, K.; Kotzerke, J. Dual-time-point 64 Cu-PSMA-617-PET/CT in patients suffering from prostate cancer. J. Labelled Comp. Radiopharm.,  2019, 62(8), 523-532.
[http://dx.doi.org/10.1002/jlcr.3745] [PMID: 31042811] 
[59] 
Grubmüller, B.; Baum, R.P.; Capasso, E.; Singh, A.; Ahmadi, Y.; Knoll, P.; Floth, A.; Righi, S.; Zandieh, S.; Meleddu, C.; Shariat, S.F.; Klingler, H.C.; Mirzaei, S. 64Cu-PSMA-617 PET/CT imaging of prostate adenocarcinoma: first in-human studies. Cancer Biother. Radiopharm.,  2016, 31(8), 277-286.
[http://dx.doi.org/10.1089/cbr.2015.1964] [PMID: 27715146] 
[60] 
Kim, K.; Kwon, H.; Choi, D.; Lim, T.; Minn, I.; Son, S.-H.; Byun, Y. Design and synthesis of dye-conjugated hepsin inhibitors. Bioorg. Chem.,  2019, 89, 102990.
[http://dx.doi.org/10.1016/j.bioorg.2019.102990] [PMID: 31136899] 
[61] 
Chen, Y.; Pullambhatla, M.; Banerjee, S.R.; Byun, Y.; Stathis, M.; Rojas, C.; Slusher, B.S.; Mease, R.C.; Pomper, M.G. Synthesis and biological evaluation of low molecular weight fluorescent imaging agents for the prostate-specific membrane antigen. Bioconjug. Chem.,  2012, 23(12), 2377-2385.
[http://dx.doi.org/10.1021/bc3003919] [PMID: 23157641] 
[62] 
Kwon, Y.-D.; Oh, J.-M.; La, M.T.; Chung, H.-J.; Lee, S.J.; Chun, S.; Lee, S.-H.; Jeong, B.-H.; Kim, H.-K. Synthesis and evaluation of multifunctional fluorescent inhibitors with synergistic interaction of prostate-specific membrane antigen and hypoxia for prostate cancer. Bioconjug. Chem.,  2019, 30(1), 90-100.
[http://dx.doi.org/10.1021/acs.bioconjchem.8b00767] [PMID: 30485073] 
[63] 
Milosevic, M.; Warde, P.; Ménard, C.; Chung, P.; Toi, A.; Ishkanian, A.; McLean, M.; Pintilie, M.; Sykes, J.; Gospodarowicz, M.; Catton, C.; Hill, R.P.; Bristow, R. Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer. Clin. Cancer Res.,  2012, 18(7), 2108-2114.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-2711] [PMID: 22465832] 
[64] 
Zha, Z.; Zhu, L.; Liu, Y.; Du, F.; Gan, H.; Qiao, J.; Kung, H.F. Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging. Nucl. Med. Biol.,  2011, 38(4), 501-508.
[http://dx.doi.org/10.1016/j.nucmedbio.2010.11.001] [PMID: 21531287] 
[65] 
Kwon, Y.-D.; Lee, J.Y.; La, M.T.; Lee, S.J.; Lee, S.-H.; Park, J.H.; Kim, H.-K. Novel multifunctional 18F-labelled PET tracer with prostate-specific membrane antigen-targeting and hypoxia-sensitive moieties. Eur. J. Med. Chem.,  2020, 189, 112099.
[http://dx.doi.org/10.1016/j.ejmech.2020.112099] [PMID: 32014792] 
[66] 
Jacobs, M.J.; Schneider, G.; Blank, K.G. Mechanical reversibility of strain-promoted azide-alkyne cycloaddition reactions. Angew. Chem. Int. Ed. Engl.,  2016, 55(8), 2899-2902.
[http://dx.doi.org/10.1002/anie.201510299] [PMID: 26806106] 
[67] 
Jayaprakash, S.; Wang, X.; Heston, W.D.; Kozikowski, A.P. Design and synthesis of a PSMA inhibitor-doxorubicin conjugate for targeted prostate cancer therapy. ChemMedChem,  2006, 1(3), 299-302.
[http://dx.doi.org/10.1002/cmdc.200500044] [PMID: 16892363] 
[68] 
Subedi, M.; Minn, I.; Chen, J.; Kim, Y.; Ok, K.; Jung, Y.W.; Pomper, M.G.; Byun, Y. Design, synthesis and biological evaluation of PSMA/hepsin-targeted heterobivalent ligands. Eur. J. Med. Chem.,  2016, 118, 208-218.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.033] [PMID: 27128184] 
[69] 
Klezovitch, O.; Chevillet, J.; Mirosevich, J.; Roberts, R.L.; Matusik, R.J.; Vasioukhin, V. Hepsin promotes prostate cancer progression and metastasis. Cancer Cell,  2004, 6(2), 185-195.
[http://dx.doi.org/10.1016/j.ccr.2004.07.008] [PMID: 15324701] 
[70] 
Katz, B.A.; Luong, C.; Ho, J.D.; Somoza, J.R.; Gjerstad, E.; Tang, J.; Williams, S.R.; Verner, E.; Mackman, R.L.; Young, W.B.; Sprengeler, P.A.; Chan, H.; Mortara, K.; Janc, J.W.; McGrath, M.E. Dissecting and designing inhibitor selectivity determinants at the S1 site using an artificial Ala190 protease (Ala190 uPA). J. Mol. Biol.,  2004, 344(2), 527-547.
[http://dx.doi.org/10.1016/j.jmb.2004.09.032] [PMID: 15522303] 
[71] 
Olszewski, R.T.; Bukhari, N.; Zhou, J.; Kozikowski, A.P.; Wroblewski, J.T.; Shamimi-Noori, S.; Wroblewska, B.; Bzdega, T.; Vicini, S.; Barton, F.B.; Neale, J.H. NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR. J. Neurochem.,  2004, 89(4), 876-885.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02358.x] [PMID: 15140187] 
[72] 
Yuan, Z.; Nodwell, M.B.; Yang, H.; Malik, N.; Merkens, H.; Bénard, F.; Martin, R.E.; Schaffer, P.; Britton, R. Site-selective, late-stage C-H 18 F-fluorination on unprotected peptides for positron emission tomography imaging. Angew. Chem. Int. Ed. Engl.,  2018, 57(39), 12733-12736.
[http://dx.doi.org/10.1002/anie.201806966] [PMID: 30086209] 
[73] 
Yuan, Z.; Yang, H.; Malik, N.; Čolović, M.; Weber, D.S.; Wilson, D.; Bénard, F.; Martin, R.E.; Warren, J.J.; Schaffer, P.; Britton, R. Electrostatic effects accelerate decatungstate-catalyzed C–H fluorination using [18F]- and [19F]NFSI in small molecules and peptide mimics. ACS Catal.,  2019, 9(9), 8276-8284.
[http://dx.doi.org/10.1021/acscatal.9b02220] 
[74] 
Liu, T.; Liu, C.; Xu, X.; Liu, F.; Guo, X.; Li, N.; Wang, X.; Yang, J.; Yang, X.; Zhu, H.; Yang, Z. Preclinical evaluation and pilot clinical study of Al18F-PSMA-BCH for prostate cancer PET imaging. J. Nucl. Med.,  2019, 60(9), 1284-1292.
[http://dx.doi.org/10.2967/jnumed.118.221671] [PMID: 30796170] 
[75] 
Harada, N.; Kimura, H.; Ono, M.; Saji, H. Preparation of asymmetric urea derivatives that target prostate-specific membrane antigen for SPECT imaging. J. Med. Chem.,  2013, 56(20), 7890-7901.
[http://dx.doi.org/10.1021/jm400895s] [PMID: 24063417] 
[76] 
Banerjee, S.R.; Pullambhatla, M.; Foss, C.A.; Nimmagadda, S.; Ferdani, R.; Anderson, C.J.; Mease, R.C.; Pomper, M.G. 64Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer. J. Med. Chem.,  2014, 57(6), 2657-2669.
[http://dx.doi.org/10.1021/jm401921j] [PMID: 24533799] 
[77] 
Hillier, S.M.; Maresca, K.P.; Lu, G.; Merkin, R.D.; Marquis, J.C.; Zimmerman, C.N.; Eckelman, W.C.; Joyal, J.L.; Babich, J.W. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J. Nucl. Med.,  2013, 54(8), 1369-1376.
[http://dx.doi.org/10.2967/jnumed.112.116624] [PMID: 23733925] 
[78] 
Tykvart, J.; Schimer, J.; Jančařík, A.; Bařinková, J.; Navrátil, V.; Starková, J.; Šrámková, K.; Konvalinka, J.; Majer, P.; Šácha, P. Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II. J. Med. Chem.,  2015, 58(10), 4357-4363.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00278] [PMID: 25923815] 
[79] 
Youn, S.; Kim, K.I.; Ptacek, J.; Ok, K.; Novakova, Z.; Kim, Y.; Koo, J.; Barinka, C.; Byun, Y. Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: synthesis and structural characterization. Bioorg. Med. Chem. Lett.,  2015, 25(22), 5232-5236.
[http://dx.doi.org/10.1016/j.bmcl.2015.09.062] [PMID: 26459214] 
[80] 
Mosayebnia, M.; Hajimahdi, Z.; Beiki, D.; Rezaeianpour, M.; Hajiramezanali, M.; Geramifar, P.; Sabzevari, O.; Amini, M.; Hatamabadi, D.; Shahhosseini, S. Design, synthesis, radiolabeling and biological evaluation of new urea-based peptides targeting prostate specific membrane antigen. Bioorg. Chem.,  2020, 99, 103743.
[http://dx.doi.org/10.1016/j.bioorg.2020.103743] [PMID: 32217372] 
[81] 
Huang, S.S.; Wang, X.; Zhang, Y.; Doke, A.; DiFilippo, F.P.; Heston, W.D. Improving the biodistribution of PSMA-targeting tracers with a highly negatively charged linker. Prostate,  2014, 74(7), 702-713.
[http://dx.doi.org/10.1002/pros.22789] [PMID: 24615708] 
[82] 
Wurzer, A.; Pollmann, J.; Schmidt, A.; Reich, D.; Wester, H.-J.; Notni, J. Molar activity of Ga-68 labeled PSMA inhibitor conjugates determines PET imaging results. Mol. Pharm.,  2018, 15(9), 4296-4302.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00602] [PMID: 30011372] 
[83] 
Liolios, C.; Schäfer, M.; Haberkorn, U.; Eder, M.; Kopka, K. Novel bispecific PSMA/GRPr targeting radioligands with optimized pharmacokinetics for improved PET imaging of prostate cancer. Bioconjug. Chem.,  2016, 27(3), 737-751.
[http://dx.doi.org/10.1021/acs.bioconjchem.5b00687] [PMID: 26726823] 
[84] 
Stenberg, V.Y.; Juzeniene, A.; Chen, Q.; Yang, X.; Bruland, Ø.S.; Larsen, R.H. Preparation of the alpha-emitting prostate-specific membrane antigen targeted radioligand [212 Pb]Pb-NG001 for prostate cancer. J. Labelled Comp. Radiopharm.,  2020, 63(3), 129-143.
[http://dx.doi.org/10.1002/jlcr.3825] [PMID: 31919866] 
[85] 
Banerjee, S.R.; Pullambhatla, M.; Shallal, H.; Lisok, A.; Mease, R.C.; Pomper, M.G. A modular strategy to prepare multivalent inhibitors of prostate-specific membrane antigen (PSMA). Oncotarget,  2011, 2(12), 1244-1253.
[http://dx.doi.org/10.18632/oncotarget.415] [PMID: 22207391] 
[86] 
Yang, X.; Mease, R.C.; Pullambhatla, M.; Lisok, A.; Chen, Y.; Foss, C.A.; Wang, Y.; Shallal, H.; Edelman, H.; Hoye, A.T.; Attardo, G.; Nimmagadda, S.; Pomper, M.G. [(18)F]fluorobenzoyllysinepentanedioic acid carbamates: new scaffolds for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA). J. Med. Chem.,  2016, 59(1), 206-218.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01268] [PMID: 26629713] 
[87] 
Merrifield, R.B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc.,  1963, 85(14), 2149-2154.
[http://dx.doi.org/10.1021/ja00897a025] 
[88] 
Cameron, A.J.; Squire, C.J.; Gérenton, A.; Stubbing, L.A.; Harris, P.W.R.; Brimble, M.A. Investigations of the key macrolactamisation step in the synthesis of cyclic tetrapeptide pseudoxylallemycin A. Org. Biomol. Chem.,  2019, 17(16), 3902-3913.
[http://dx.doi.org/10.1039/C9OB00227H] [PMID: 30941386] 
[89] 
Siow, A.; Hung, K.; Harris, P.W.R.; Brimble, M.A. Solid-phase synthesis of the peptaibol alamethicin U-22324 by using a double-linker strategy. Eur. J. Org. Chem.,  2017, 2017(2), 350-354.
[http://dx.doi.org/10.1002/ejoc.201601102] 
[90] 
Carter, R.E.; Feldman, A.R.; Coyle, J.T. Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc. Natl. Acad. Sci. USA,  1996, 93(2), 749-753.
[http://dx.doi.org/10.1073/pnas.93.2.749] [PMID: 8570628] 
[91] 
Barinka, C.; Rinnová, M.; Sácha, P.; Rojas, C.; Majer, P.; Slusher, B.S.; Konvalinka, J. Substrate specificity, inhibition and enzymological analysis of recombinant human glutamate carboxypeptidase II. J. Neurochem.,  2002, 80(3), 477-487.
[http://dx.doi.org/10.1046/j.0022-3042.2001.00715.x] [PMID: 11905994] 
[92] 
Aggarwal, S.; Singh, P.; Topaloglu, O.; Isaacs, J.T.; Denmeade, S.R. A dimeric peptide that binds selectively to prostate-specific membrane antigen and inhibits its enzymatic activity. Cancer Res.,  2006, 66(18), 9171-9177.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1520] [PMID: 16982760] 
[93] 
Aggarwal, S.; Janssen, S.; Wadkins, R.M.; Harden, J.L.; Denmeade, S.R. A combinatorial approach to the selective capture of circulating malignant epithelial cells by peptide ligands. Biomaterials,  2005, 26(30), 6077-6086.
[http://dx.doi.org/10.1016/j.biomaterials.2005.03.040] [PMID: 15907998] 
[94] 
Wrighton, N.C.; Balasubramanian, P.; Barbone, F.P.; Kashyap, A.K.; Farrell, F.X.; Jolliffe, L.K.; Barrett, R.W.; Dower, W.J. Increased potency of an erythropoietin peptide mimetic through covalent dimerization. Nat. Biotechnol.,  1997, 15(12), 1261-1265.
[http://dx.doi.org/10.1038/nbt1197-1261] [PMID: 9359108] 
[95] 
Lupold, S.E.; Rodriguez, R. Disulfide-constrained peptides that bind to the extracellular portion of the prostate-specific membrane antigen. Mol. Cancer Ther.,  2004, 3(5), 597-603.
[PMID: 15141017] 
[96] 
Shen, D.; Xie, F.; Edwards, W.B. Evaluation of phage display discovered peptides as ligands for prostate-specific membrane antigen (PSMA). PLoS One,  2013, 8(7), e68339.
[http://dx.doi.org/10.1371/journal.pone.0068339] [PMID: 23935860] 
[97] 
Conway, R.E.; Rojas, C.; Alt, J.; Nováková, Z.; Richardson, S.M.; Rodrick, T.C.; Fuentes, J.L.; Richardson, N.H.; Attalla, J.; Stewart, S.; Fahmy, B.; Barinka, C.; Ghosh, M.; Shapiro, L.H.; Slusher, B.S. Prostate-specific membrane antigen (PSMA)-mediated laminin proteolysis generates a pro-angiogenic peptide. Angiogenesis,  2016, 19(4), 487-500.
[http://dx.doi.org/10.1007/s10456-016-9521-x] [PMID: 27387982] 
[98] 
Brehmer, B.; Biesterfeld, S.; Jakse, G. Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue. Prostate Cancer Prostatic Dis.,  2003, 6(3), 217-222.
[http://dx.doi.org/10.1038/sj.pcan.4500657] [PMID: 12970724] 
[99] 
Ahn, T.; Roberts, M.J.; Abduljabar, A.; Joshi, A.; Perera, M.; Rhee, H.; Wood, S.; Vela, I. A review of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in renal cell carcinoma (RCC). Mol. Imaging Biol.,  2019, 21(5), 799-807.
[http://dx.doi.org/10.1007/s11307-018-01307-0] [PMID: 30617728] 
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DOI https://dx.doi.org/10.2174/0929867327666201006153847	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Evolution of Peptide-Based Prostate-Specific Membrane Antigen (PSMA) Inhibitors: An Approach to Novel Prostate Cancer Therapeutics

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