ReviewCurrent pharmaceutical biotechnology2008
Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity.
Review in Current pharmaceutical biotechnology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 102 citations in OpenAlex.
- Development of Chimeric Ribonuclease A Inhibitor for Molecular Biology Applications: SUMO Fusion as an Engineering Strategy.Current issues in molecular biology · 2026Article
- RNase A is inhibited by the cysteine-rich protein thionein but not by the metal-containing form metallothionein.Molecular and cellular biochemistry · 2026Article
- Onconase Induces Apoptosis in Dabrafenib-Resistant Melanoma Cell Lines Through Dysregulation of ROS Homeostasis, Antioxidant Protein Expression, and Mitochondrial Dynamics.International journal of molecular sciences · 2026Article
- Novel Organomineral Complex with Prolonged Antitumor Action.International journal of molecular sciences · 2025Article
- Review
- Protein Oligomerization.International journal of molecular sciences · 2023Article
- Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections.International journal of molecular sciences · 2022Review
- Emerging biological functions of ribonuclease 1 and angiogenin.Critical reviews in biochemistry and molecular biology · 2022Review
- Bovine Pancreatic RNase A: An Insight into the Mechanism of Antitumor Activity In Vitro and In Vivo.Pharmaceutics · 2022Article
- Exploring the RNase A scaffold to combine catalytic and antimicrobial activities. Structural characterization of RNase 3/1 chimeras.Frontiers in molecular biosciences · 2022Article
- Structure-Based Design of an RNase Chimera for Antimicrobial Therapy.International journal of molecular sciences · 2021Article
- Ribonuclease zymogen induces cytotoxicity upon HIV-1 infection.AIDS research and therapy · 2021Article
- Dimerization of Human Angiogenin and of Variants Involved in Neurodegenerative Diseases.International journal of molecular sciences · 2021Article
- Specific Targeting of Recombinant Human Pancreatic Ribonuclease 1 using Gonadotropin-Releasing Hormone Targeting Peptide toward Gonadotropin-Releasing Hormone Receptor-Positive Cancer Cells.Iranian journal of medical sciences · 2021Article
- Trans-acting regulators of ribonuclease activity.Journal of microbiology (Seoul, Korea) · 2021Review
- RNase A Domain-Swapped Dimers Produced Through Different Methods: Structure-Catalytic Properties and Antitumor Activity.Life (Basel, Switzerland) · 2021Article
- Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection.Frontiers in cell and developmental biology · 2020Review
- Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability.International journal of molecular sciences · 2019Article
- Circular zymogens of human ribonuclease 1.Protein science : a publication of the Protein Society · 2019Article
- Esterification Delivers a Functional Enzyme into a Human Cell.ACS chemical biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Onconase (ONC) is an amphibian member of the bovine pancreatic ribonuclease (RNase A) superfamily that exhibits innate antitumoral activity. ONC has been granted both orphan-drug and fast-track status by the U.S. Food and Drug Administration for the treatment of malignant mesothelioma, and is poised to become the first chemotherapeutic agent based on a ribonuclease. Investigations into the mechanism of ribonuclease-based cytotoxicity have elucidated several important determinants for cytotoxicity, including efficient deliverance of ribonucleolytic activity to the cytosol and preservation of conformation stability. Nevertheless, the most striking similarity between ONC and bovine seminal ribonuclease, another naturally cytotoxic ribonuclease, is their insensitivity to inhibition by the potent cytosolic ribonuclease inhibitor protein (RI). RI typically binds to its ribonuclease ligands with femtomolar affinity--an extraordinary feat considering the modest sequence identity among the bound ribonucleases. Mammalian ribonucleases such as RNase A or its human homologue, RNase 1, have the potential to be more attractive chemotherapeutic agents than ONC owing to their higher catalytic activity, low potential for immunogenicity, favorable tissue distribution, and high therapeutic index, but are limited by their sensitivity to RI. These non-toxic mammalian ribonucleases can be transformed into potent cytotoxins by engendering them with RI-evasion using protein engineering strategies such as site-directed mutagenesis, multimerization, fusion to a targeting moiety, and chemical modification. In several instances, these engineered ribonucleases exhibit greater cytotoxicity in vitro than does ONC. Herein, we review the biochemical characteristics of RIribonuclease complexes and progress towards the development of mammalian ribonuclease-based chemotherapeutics through the elicitation of RI-evasion.
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Registered trials
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.