Evidence map›Paper›PMID 27314340›Full record

ReviewInternational journal of molecular sciences2016

Kynurenine Aminotransferase Isozyme Inhibitors: A Review.

Alireza Nematollahi, Guanchen Sun, Gayan S Jayawickrama, W Bret Church

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 17% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Duplication of a conserved mitochondrial enzyme gene arms parasitoid wasps with venom cytotoxicity and oogenesis regulation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Kynurenine Metabolites in CSF and Plasma in Healthy Males.International journal of tryptophan research : IJTR · 2024
    Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. A Role for Xanthurenic Acid in the Control of Brain Dopaminergic Activity.International journal of molecular sciences · 2021
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Alireza NematollahiGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. anem7250@uni.sydney.edu.au.
Guanchen SunGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. gsun2866@uni.sydney.edu.au.
Gayan S JayawickramaGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. gjay8197@uni.sydney.edu.au.
W Bret ChurchGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. bret.church@sydney.edu.au.
University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kynurenine aminotransferase isozymes (KATs 1-4) are members of the pyridoxal-5'-phosphate (PLP)-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN) to kynurenic acid (KYNA), a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS) diseases, the KATs are prominent targets in the quest to treat neurodegenerative and cognitive impairment disorders. Recent studies suggest that inhibiting these enzymes would produce effects beneficial to patients with these conditions, as abnormally high levels of KYNA are observed. KAT-1 and KAT-3 share the highest sequence similarity of the isozymes in this family, and their active site pockets are also similar. Importantly, KAT-2 has the major role of kynurenic acid production (70%) in the human brain, and it is considered therefore that suitable inhibition of this isozyme would be most effective in managing major aspects of CNS diseases. Human KAT-2 inhibitors have been developed, but the most potent of them, chosen for further investigations, did not proceed in clinical studies due to the cross toxicity caused by their irreversible interaction with PLP, the required cofactor of the KAT isozymes, and any other PLP-dependent enzymes. As a consequence of the possibility of extensive undesirable adverse effects, it is also important to pursue KAT inhibitors that reversibly inhibit KATs and to include a strategy that seeks compounds likely to achieve substantial interaction with regions of the active site other than the PLP. The main purpose of this treatise is to review the recent developments with the inhibitors of KAT isozymes. This treatise also includes analyses of their crystallographic structures in complex with this enzyme family, which provides further insight for researchers in this and related studies.

Indexed as

AnimalsBinding SitesEnzyme InhibitorsHumansModels, MolecularMolecular ConformationMolecular StructureProtein BindingQuantitative Structure-Activity RelationshipTransaminasesEnzyme Inhibitorskynurenine-oxoglutarate transaminaseTransaminasescognitive disordersKYNAkynurenine aminotransferasepyridoxal 5′-phosphateschizophrenia

Identifiers

PMID27314340
PMCPMC4926479
OpenAlexW2441834749

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.