ArticleThe Journal of pharmacology and experimental therapeutics2013
Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.Neuroscience and biobehavioral reviews · 2018Pooled it
- Novel macrocyclic peptidomimetics targeting the insulin-regulated aminopeptidase (IRAP): design, synthesis and evaluation.RSC medicinal chemistry · 2025Article
- Comparative analysis of small molecule and growth factor-derived human induced pluripotent stem cell-derived hepatocyte-like cells.Frontiers in cell and developmental biology · 2025Article
- Angiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition.Biomedicines · 2024Article
- Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.Stem cell research & therapy · 2022Article
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.Brain sciences · 2021Article
- Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies.Annals of medicine and surgery (2012) · 2021Article
- Robust expansion and functional maturation of human hepatoblasts by chemical strategy.Stem cell research & therapy · 2021Article
- HGF and MET: From Brain Development to Neurological Disorders.Frontiers in cell and developmental biology · 2021Review
- Brain angiotensin II and angiotensin IV receptors as potential Alzheimer's disease therapeutic targets.GeroScience · 2020Review
- Hepatocyte-like cells derived from human induced pluripotent stem cells using small molecules: implications of a transcriptomic study.Stem cell research & therapy · 2020Article
- Inflammation-related plasma and CSF biomarkers for multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- From Angiotensin IV to Small Peptidemimetics Inhibiting Insulin-Regulated Aminopeptidase.Frontiers in pharmacology · 2020Review
- Structural Basis of Inhibition of Human Insulin-Regulated Aminopeptidase (IRAP) by Aryl Sulfonamides.ACS omega · 2018Article
- Within the Brain: The Renin Angiotensin System.International journal of molecular sciences · 2018Review
- Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells.Stem cell reports · 2015Article
- Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure.Frontiers in cellular neuroscience · 2015Article
- 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
- Role of angiotensin modulation in primary headaches.Current pain and headache reports · 2014Review
- A Role for the Brain RAS in Alzheimer's and Parkinson's Diseases.Frontiers in endocrinology · 2013Review
Corrections and comments
- Expression of concern · 2021-09-22Concerns/Issues about Image ·
- Expression of concern
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Angiotensin IV (AngIV: VYIHPF)-related peptides have long been recognized as procognitive agents with potential as antidementia therapeutics. Their development as useful therapeutics, however, has been limited by physiochemical properties that make them susceptible to metabolic degradation and impermeable to gut and blood-brain barriers. A previous study demonstrated that the core structural information required to impart the procognitive activity of the AngIV analog, norleucine(1)-angiotensin IV, resides in its three N-terminal amino acids, Nle-Tyr-Ile. The goal of this project was to chemically modify this tripeptide in such a way to enhance its metabolic stability and barrier permeability to produce a drug candidate with potential clinical utility. Initial results demonstrated that several N- and C-terminal modifications lead to dramatically improved stability while maintaining the capability to reverse scopolamine-induced deficits in Morris water maze performance and augment hippocampal synaptogenesis. Subsequent chemical modifications, which were designed to increase hydrophobicity and decrease hydrogen bonding, yielded an orally active, blood-barrier permeant, metabolically stabilized analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa), that exhibits excellent antidementia activity in the scopolamine and aged rat models and marked synaptogenic activity. These data suggest that dihexa may have therapeutic potential as a treatment of disorders, such as Alzheimer's disease, where augmented synaptic connectivity may be beneficial.
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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.