ArticleCell communication and signaling : CCS2019
Neuropilin-1 drives tumor-specific uptake of chlorotoxin.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Chlorotoxin suppresses melanoma vasculogenic mimicry via LINC01235/miR-128-3p/YY1/ VEGFR2/NRP1 axis.iScience · 2026Article
- Peptides as multifunctional linchpins in targeted drug conjugates.RSC medicinal chemistry · 2026Review
- Nrp1 Signaling Reprograms Glutathione Metabolism to Drive Mitochondrial Dysfunction in Severe Asthma.Antioxidants (Basel, Switzerland) · 2026Article
- Directed evolution of chlorotoxin enhances MMP-2 recognition and improves CAR-T-cell activity in glioblastoma modelsFrontiers in bioengineering and biotechnology · 2026Article
- Diagnostic and Therapeutic Approaches for Glioblastoma and Neuroblastoma Cancers Using Chlorotoxin Nanoparticles.Cancers · 2023Review
- Peptides with Diverse Functions from Scorpion Venom: A Great Opportunity for the Treatment of a Wide Variety of Diseases.Iranian biomedical journal · 2023Article
- Chlorotoxin and Lung Cancer: A Targeting Perspective for Drug Delivery.Pharmaceutics · 2022Article
- Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide.Molecules (Basel, Switzerland) · 2022Article
- Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes.Clinical medicine insights. Endocrinology and diabetes · 2021Review
- Structural basis for the binding of the cancer targeting scorpion toxin, ClTx, to the vascular endothelia growth factor receptor neuropilin-1.Current research in structural biology · 2021Article
- Receptor-Targeted Fluorescence-Guided Surgery With Low Molecular Weight Agents.Frontiers in oncology · 2021Review
- Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChlorotoxin (Cltx) isolated from scorpion venom is an established tumor targeting and antiangiogenic peptide. Radiolabeled Cltx therapeutic (
methodsA peptide-drug conjugate (ER-472) composed of Cltx linked to cryptophycin as warhead was developed as a tool to probe the molecular target and mechanism of action of Cltx, using multiple xenograft models.
resultsNeuropilin-1 (NRP1), an endocytic receptor on tumor and endothelial cells, was identified as a novel Cltx target, and NRP1 binding by Cltx increased drug uptake into tumor. Metabolism of Cltx to peptide bearing free C-terminal arginine, a prerequisite for NRP1 binding, took place in the tumor microenvironment, while native scorpion Cltx with amidated C-terminal arginine did not bind NRP1, and instead acts as a cryptic peptide. Antitumor activity of ER-472 in xenografts correlated to tumor NRP1 expression. Potency was significantly reduced by treatment with NRP1 blocking antibodies or knockout in tumor cells, confirming a role for NRP1-binding in ER-472 activity. Higher cryptophycin metabolite levels were measured in NRP1-expressing tumors, evidence of NRP1-mediated enhanced drug uptake and presumably responsible for the superior antitumor efficacy.
conclusionsNRP1 was identified as a novel Cltx target which enhances tumor drug uptake. This finding should facilitate tumor selection for chlorotoxin-based therapeutics and diagnostics.
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