Evidence map›Paper›PMID 34648893›Full record

ArticleJournal of biotechnology2021

Target-directed evolution of novel modulators of the dopamine transporter in Lobelia cardinalis hairy root cultures.

Dennis T Rogers, Francois Pomerleau, Zachary Kelley, Dustin Brown, Bert Lynn, Greg A Gerhardt, John Littleton

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 88% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

7 authors at 2 institutions in 1 country.

Dennis T RogersNaprogenix™, UK-AsTeCC, 145 Graham Avenue, Lexington, KY 40506-0286, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA. Electronic address: dennistrogers@naprogenix.com.
Francois PomerleauCollege of Medicine, Department of Neuroscience, University of Kentucky Chandler Medical Center, 800 Rose St, Lexington, KY 40536-0298, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA; College of Medicine, Brain Restoration Center, University of Kentucky Chandler Medical Center, 800 Rose St., Lexington, KY 40536-0298, USA; College of Medicine, Center for Microelectrode Technology, University of Kentucky Chandler Medical Center, 800 Rose St, Lexington, KY 40536-0298, USA.
Zachary KelleyDepartment of Chemistry, University of Kentucky, Lexington, KY 40536-9983, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA.
Dustin BrownCollege of Medicine, Department of Neuroscience, University of Kentucky Chandler Medical Center, 800 Rose St, Lexington, KY 40536-0298, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA.
Bert LynnDepartment of Chemistry, University of Kentucky, Lexington, KY 40536-9983, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA.
Greg A GerhardtCollege of Medicine, Department of Neuroscience, University of Kentucky Chandler Medical Center, 800 Rose St, Lexington, KY 40536-0298, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA; College of Medicine, Department of Psychiatry, University of Kentucky Chandler Medical Center, 245 Fountain Ct, Lexington, KY 40509, USA; College of Medicine, Department of Neurosurgery, University of Kentucky Chandler Medical Center, 800 Rose St, Lexington, KY 40536-0298, USA; College of Medicine, Brain Restoration Center, University of Kentucky Chandler Medical Center, 800 Rose St., Lexington, KY 40536-0298, USA; College of Medicine, Center for Microelectrode Technology, University of Kentucky Chandler Medical Center, 800 Rose St, Lexington, KY 40536-0298, USA.
John LittletonNaprogenix™, UK-AsTeCC, 145 Graham Avenue, Lexington, KY 40506-0286, USA; College of Medicine, Department of Neurology, University of Kentucky Chandler Medical Center, 740 S. Limestone, Lexington, KY 40536-0298, USA; College of Arts and Sciences, Department of Psychology, University of Kentucky, Kastle Hall, Lexington, KY 40506-0044, USA.
Albert B. Chandler Hospital · USUniversity of Kentucky · US

Funding

Novel modulators of the dopamine transporter for alcohol and nicotine use disordersR44AA025804 · NIAAA · NAPROGENIX, INC · PI BURKLOW, CINDY ANN · 2016 to 2022
$4.0M
Selection-driven plant metabolites for treatment of CNS diseasesR44AA018226 · NIAAA · NAPROGENIX, INC · PI LITTLETON, JOHN M. · 2013 to 2015
$1.1M
NIAAA NIH HHS R44 AA018226NIAAA NIH HHS R44 AA025804
6 · The paper itself

Abstract

The dopamine transporter (DAT) is targeted in substance use disorders (SUDs), and "non-classical"" DAT inhibitors with low abuse potential are therapeutic candidates. Lobinaline, from Lobelia cardinalis, is an atypical DAT inhibitor lead. Chemical synthesis of lobinaline is challenging; thus, "target-directed evolution" was used for lead optimization. A target protein is expressed in plant cells, and a mutant cell population is selected under conditions where target protein functional inhibition confers a survival advantage. Surviving mutants are "mined" for the targeted activity. Applied to a mutant L. cardinalis cell population expressing the human DAT, we identified 20 mutants overproducing DAT inhibitors. Microanalysis prioritized novel lobinaline derivatives, and we first investigated the more water-soluble lobinaline N-oxide. It inhibited rat synaptosomal [3H]DA uptake with an IC

Indexed as

Dopamine Plasma Membrane Transport ProteinsLobeliaAnimalsCorpus StriatumDopamineRatsSynaptosomesDopamineDopamine Plasma Membrane Transport ProteinsActivation tagging mutagenesisChrono-amperometryDirected evolutionDopamine transport inhibitorsLobinalineSubstance use disorders

Identifiers

PMID34648893
PMCPMC8657075
OpenAlexW3206664848

What OpenQuestion holds

Textmetadata
LicenceTDM
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.