ArticleNature biomedical engineering2026
Discovery of high-affinity ligands for prostatic acid phosphatase via DNA-encoded library screening enables targeted cancer therapy.
Article in Nature biomedical engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- From DNA-Encoded Chemistry to Tumor-Targeted Small Molecule Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeted extracellular vesicle-photoimmunotherapy remodels stromal-immune microenvironment to boost chemo-immunotherapy in preclinical models.Cell reports. Medicine · 2026Article
- Prostatic acid phosphatase: a rediscovered target in prostate cancer.Nature reviews. Urology · 2026Article
- Recent Advances in GPCR Ligand Discovery Using DNA-Encoded Library Technology: From Affinity Binding to Functional Bias and Allosteric Modulation.ACS medicinal chemistry letters · 2026Review
- Beyond conceptual advances in cancer therapies.Nature biomedical engineering · 2026Article
- ACP3-targeted PET imaging agents based on small-molecule ligands for prostate cancer diagnostics and theranostics.American journal of nuclear medicine and molecular imaging · 2026Article
- 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
Corrections and comments
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Authors and funding
16 authors.
Funding
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Abstract
Improving the specificity of prostate cancer treatment requires ligands that bind selectively and with ultra-high affinity to tumour-associated targets absent from healthy tissues. Prostatic acid phosphatase has emerged as an alternative target to prostate-specific membrane antigen, as it is expressed in a broader subset of prostate cancers and is not detected in healthy organs such as the salivary glands and kidneys. Here, to discover selective binders to prostatic acid phosphatase, we constructed two DNA-encoded chemical libraries comprising over 6.7 million small molecules based on proline and phenylalanine scaffolds. Screening against the purified human prostatic acid phosphatase yielded OncoACP3, a small organic ligand with picomolar binding affinity. When radiolabelled with lutetium-177, OncoACP3 selectively accumulated in enzyme-expressing tumours with a long residence time (biological half-life greater than 72 h) and a high tumour-to-blood ratio (>148 at 2 h after administration). Lutetium-177-labelled OncoACP3 cured tumours in mice at low, well-tolerated doses. Its conjugation to the cytotoxic agent monomethyl auristatin E facilitated tumour-selective payload deposition, resulting in potent anti-tumour activity. The modular structure of OncoACP3 supports flexible payload delivery for the targeted treatment of metastatic prostate cancer.
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