A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications
The treatment of metastatic Castration Resistant Prostate Cancer (mCRPC) by targeting Prostate Specific Membrane Antigen (PSMA), that is ubiquitously expressed on malicious cells, using177Lu-PSMA-617, has been showing great potential. Considering the promising results from Radioligand Therapy (RLT)...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | European Journal of Medicinal Chemistry Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417422000565 |
| _version_ | 1811294638000046080 |
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| author | K.S. Ajish Kumar Anupam Mathur |
| author_facet | K.S. Ajish Kumar Anupam Mathur |
| author_sort | K.S. Ajish Kumar |
| collection | DOAJ |
| description | The treatment of metastatic Castration Resistant Prostate Cancer (mCRPC) by targeting Prostate Specific Membrane Antigen (PSMA), that is ubiquitously expressed on malicious cells, using177Lu-PSMA-617, has been showing great potential. Considering the promising results from Radioligand Therapy (RLT) studies conducted at multiple centres, 177Lu-PSMA-617, is being considered for FDA approval. The organic ligand, PSMA-617, is therefore in great demand, but it is also an expensive pharmaceutical precursor. We demonstrate here a convenient synthetic protocol for PSMA-617, using a solution phase method. Both, linear and convergent synthetic strategies were explored to affirm that the later approach furnished the target in better yield. The protocol presented here involves the use of commercially and economically viable reagents together with flow reactor based metal catalyzed hydrogenation as vital step. Using the method portrayed, PSMA-617 with purity >99.5% was achieved, while, radiolabelling with 177Lu afforded, 177Lu-PSMA-617 with radiochemical purity >98%, which is adequate for therapeutic applications. 177Lu-PSMA-617 prepared using the synthesized ligand showed parity in purity against that made from commercial equivalent. |
| first_indexed | 2024-04-13T05:20:25Z |
| format | Article |
| id | doaj.art-9a81b1d6dd1a4816865ae82e48f1f23b |
| institution | Directory Open Access Journal |
| issn | 2772-4174 |
| language | English |
| last_indexed | 2024-04-13T05:20:25Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj.art-9a81b1d6dd1a4816865ae82e48f1f23b2022-12-22T03:00:46ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742022-12-016100084A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applicationsK.S. Ajish Kumar0Anupam Mathur1Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India; Corresponding author. Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, 400085, India.Radiopharmaceuticals Program, Board of Radiation and Isotope Technology, Navi Mumbai, 400703, IndiaThe treatment of metastatic Castration Resistant Prostate Cancer (mCRPC) by targeting Prostate Specific Membrane Antigen (PSMA), that is ubiquitously expressed on malicious cells, using177Lu-PSMA-617, has been showing great potential. Considering the promising results from Radioligand Therapy (RLT) studies conducted at multiple centres, 177Lu-PSMA-617, is being considered for FDA approval. The organic ligand, PSMA-617, is therefore in great demand, but it is also an expensive pharmaceutical precursor. We demonstrate here a convenient synthetic protocol for PSMA-617, using a solution phase method. Both, linear and convergent synthetic strategies were explored to affirm that the later approach furnished the target in better yield. The protocol presented here involves the use of commercially and economically viable reagents together with flow reactor based metal catalyzed hydrogenation as vital step. Using the method portrayed, PSMA-617 with purity >99.5% was achieved, while, radiolabelling with 177Lu afforded, 177Lu-PSMA-617 with radiochemical purity >98%, which is adequate for therapeutic applications. 177Lu-PSMA-617 prepared using the synthesized ligand showed parity in purity against that made from commercial equivalent.http://www.sciencedirect.com/science/article/pii/S2772417422000565NuclearLigandsPSMAProstateCancer |
| spellingShingle | K.S. Ajish Kumar Anupam Mathur A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications European Journal of Medicinal Chemistry Reports Nuclear Ligands PSMA Prostate Cancer |
| title | A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications |
| title_full | A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications |
| title_fullStr | A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications |
| title_full_unstemmed | A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications |
| title_short | A convenient total synthesis of PSMA-617: A prostate specific membrane antigen (PSMA) ligand for prostate cancer endotherapeutic applications |
| title_sort | convenient total synthesis of psma 617 a prostate specific membrane antigen psma ligand for prostate cancer endotherapeutic applications |
| topic | Nuclear Ligands PSMA Prostate Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2772417422000565 |
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