ArticleChemical science2024
DNA-encoded chemical libraries enable the discovery of potent PSMA-ligands with substantially reduced affinity towards the GCPIII anti-target.
Article in Chemical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Generation and characterization of novel high-affinity fully human antibodies targeting prostate-specific membrane antigen and prostatic acid phosphatase.Antibody therapeutics · 2025Article
- Phenylalanine-Based DNA-Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
10 authors.
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Abstract
Prostate-specific membrane antigen (PSMA) is a tumor-associated protein that has been successfully targeted with small organic ligands and monoclonal antibodies. Pluvicto™ is a PSMA-targeted radioligand therapeutic (RLT) recently approved by the FDA for the treatment of metastatic castration-resistant prostate cancer (2022 FDA marketing authorization). Although a large Phase III clinical trial (VISION trial) demonstrated clinical benefits in patients treated with Pluvicto™, the therapeutic window of the drug is narrowed by its undesired accumulation in healthy organs. Glutamate carboxypeptidase III (GCPIII), an enzyme sharing 70% identity with PSMA, may be responsible for the off-target accumulation of PSMA-RLTs in salivary glands and kidneys. In this work, we designed and synthesized affinity and selectivity maturation DNA-encoded chemical libraries (ASM-DELs) comprising 18'284'658 compounds that were screened in parallel against PSMA and GCPIII with the aim to identify potent and selective PSMA ligands for tumor-targeting applications. Compound A70-B104 was isolated as the most potent and selective ligand (
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