ArticleMolecular pharmaceutics2012
Targeting cell surface alpha(v)beta(3) integrin increases therapeutic efficacies of a legumain protease-activated auristatin prodrug.
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 87 citations in OpenAlex.
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- Co-delivery of Cas9 mRNA and guide RNAs for editing of LGMN gene represses breast cancer cell metastasis.Scientific reports · 2024Article
- Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment.Frontiers in pharmacology · 2024Article
- A Smart Intracellular Self-Assembling Bioorthogonal Raman Active Nanoprobe for Targeted Tumor Imaging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration.NPJ Regenerative medicine · 2023Article
- Article
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- Targeted Enzyme Activity Imaging with Quantitative Phase Microscopy.Nano letters · 2023Article
- Legumain Functions as a Transient TrkB Sheddase.International journal of molecular sciences · 2023Article
- Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration.bioRxiv : the preprint server for biology · 2023Article
- Autocrine pro-legumain promotes breast cancer metastasis via binding to integrin αvβ3.Oncogene · 2022Article
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- A Small Molecule-Drug Conjugate (SMDC) Consisting of a Modified Camptothecin Payload Linked to an αCancers · 2022Article
- Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition.Open life sciences · 2022Article
- The Mechanism of Asparagine Endopeptidase in the Progression of Malignant Tumors: A Review.Cells · 2021Review
- Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Novel monomethylauristatin E (MMAE) prodrug 8 was designed and prepared that bound cell surface glycoprotein integrin αvβ3, and was activated using legumain protease as a catalyst. Upon activation, prodrug 8 strongly induced the death of MDA-MB-435 cells that express integrin αvβ3 on cell surface. Efficacies of prodrug 8 were also determined in vivo using animal models of 4T1 murine breast cancer, D121 Lewis lung carcinoma, and MDA-MB-435 human breast cancer. The results demonstrated that prodrug 8 decreased tumor growth and metastasis effectively. In comparison to the parent cytotoxin, MMAE, and prodrug 3, prodrug 8 was less toxic to mouse white blood cells. The latter caused no loss in weight gain of mice at a dose 3 mg/kg, which is over 30 times in excess to MMAE (0.1 mg/kg). We hypothesize that overexpression and colocalization of integrin αvβ3 and legumain protease on tumor cells, tumor vasculature, and/or tumor microenvironments can be exploited to enhance the efficacy and selectivity of potent cytotoxins, such as MMAE, which is otherwise too toxic to use for therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.