ArticleThe Journal of pharmacology and experimental therapeutics2010
The angiotensin IV analog Nle-Tyr-Leu-psi-(CH2-NH2)3-4-His-Pro-Phe (norleual) can act as a hepatocyte growth factor/c-Met inhibitor.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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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
17 citing papers in PubMed, 39 citations in OpenAlex.
- Angiotensin IV does not exert prothrombotic effectsJournal of molecular and cellular cardiology plus · 2025Article
- Article
- Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2021Article
- From Angiotensin IV to Small Peptidemimetics Inhibiting Insulin-Regulated Aminopeptidase.Frontiers in pharmacology · 2020Review
- Norleual, a hepatocyte growth factor and macrophage stimulating protein dual antagonist, increases pancreatic cancer sensitivity to gemcitabine.Anti-cancer drugs · 2018Article
- Analogs of the hepatocyte growth factor and macrophage-stimulating protein hinge regions act as Met and Ron dual inhibitors in pancreatic cancer cells.Anti-cancer drugs · 2016Article
- The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.The Journal of pharmacology and experimental therapeutics · 2014Article
- Angiotensin IV is induced in experimental autoimmune encephalomyelitis but fails to influence the disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Article
- A Role for the Brain RAS in Alzheimer's and Parkinson's Diseases.Frontiers in endocrinology · 2013Review
- Central administration of angiotensin IV rapidly enhances novel object recognition among mice.Neuropharmacology · 2013Article
- HGF-MET cascade, a key target for inhibiting cancer metastasis: the impact of NK4 discovery on cancer biology and therapeutics.International journal of molecular sciences · 2013Article
- Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.The Journal of pharmacology and experimental therapeutics · 2013Article
- The brain renin-angiotensin system: a diversity of functions and implications for CNS diseases.Pflugers Archiv : European journal of physiology · 2013Review
- The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats.Brain sciences · 2012Article
- Discovery of inhibitors of insulin-regulated aminopeptidase as cognitive enhancers.International journal of hypertension · 2012Article
- Importance of the brain Angiotensin system in Parkinson's disease.Parkinson's disease · 2012Article
- Identification and development of specific inhibitors for insulin-regulated aminopeptidase as a new class of cognitive enhancers.British journal of pharmacology · 2011Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The angiotensin (Ang) IV analog norleual [Nle-Tyr-Leu-psi-(CH2-NH2)(3-4)-His-Pro-Phe] exhibits structural homology with the hinge (linker) region of hepatocyte growth factor (HGF) and is hypothesized to act as a hinge region mimic. Norleual competitively inhibited the binding of HGF to its receptor c-Met in mouse liver membranes, with an IC(50) value of 3 pM. Predictably, norleual was able to inhibit HGF-dependent signaling, proliferation, migration, and invasion in multiple cell types at concentrations in the picomolar range. Ex vivo studies demonstrated that norleual exhibited potent antiangiogenic activity, an attribute that would be predicted for a HGF/c-Met antagonist. Furthermore, norleual suppressed pulmonary colonization by B16-F10 murine melanoma cells, which are characterized by an overactive HGF/c-Met system. Together, these data suggest that AngIV analogs exert at least some of their biological activity through interference with the HGF/c-Met system and may have utility as therapeutic agents in disorders that are dependent on an intact HGF/c-Met system. Finally, the ability of norleual to induce marked biological responses in human embryonic kidney cells, which do not express insulin-responsive aminopeptidase (IRAP), coupled with the observed effects of norleual on the HGF/c-Met system, casts doubt on the physiological significance of AngIV-dependent inhibition of IRAP. [Corrected]
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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.