Evidence map›Paper›PMID 35133171›Full record

ArticleJournal of medicinal chemistry2022

Development of a Novel, Small-Molecule Brain-Penetrant Histone Deacetylase Inhibitor That Enhances Spatial Memory Formation in Mice.

Jawad B Belayet, Sarah Beamish, Mizzanoor Rahaman, Samer Alanani, Rajdeep S Virdi, David N Frick, A F M Towheedur Rahman, Joseph S Ulicki, Sreya Biswas, Leggy A Arnold and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

15 authors.

Jawad B BelayetDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Sarah BeamishDepartment of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Mizzanoor RahamanDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Samer AlananiDepartment of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Rajdeep S VirdiDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
David N FrickDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.ORCID 0000-0002-2434-7223
A F M Towheedur RahmanDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Joseph S UlickiDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Sreya BiswasDepartment of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Leggy A ArnoldDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.ORCID 0000-0003-1411-1572
M S Rashid RoniDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.ORCID 0000-0002-3105-0540
Eric Y ChengCollege of Pharmacy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas 76107, United States.ORCID 0000-0001-9336-2593
Douglas A SteeberDepartment of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
Karyn M FrickDepartment of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
M Mahmun HossainDepartment of Chemistry and Biochemistry and Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.ORCID 0000-0002-0874-4480

Funding

Mechanisms underlying memory regulation by 17beta-estradiol, canonical Wnt signaling, and BDNF in male and female miceR01MH107886 · NIMH · UNIVERSITY OF WISCONSIN MILWAUKEE · PI FRICK, KARYN M · 2016 to 2020
$1.9M
Development of ER-beta Agonists to Treat Post-Menopausal Memory DeclineR15GM118304 · NIGMS · CONCORDIA UNIVERSITY WISCONSIN · PI SEM, DANIEL S · 2015 to 2018
$820k
NIGMS NIH HHS R15 GM118304NIMH NIH HHS R01 MH107886
6 · The paper itself

Abstract

Histone acetylation is a prominent epigenetic modification linked to the memory loss symptoms associated with neurodegenerative disease. The use of existing histone deacetylase inhibitor (HDACi) drugs for treatment is precluded by their weak blood-brain barrier (BBB) permeability and undesirable toxicity. Here, we address these shortcomings by developing a new class of disulfide-based compounds, inspired by the scaffold of the FDA-approved HDACi romidepsin (FK288). Our findings indicate that our novel compound MJM-1 increases the overall level of histone 3 (H3) acetylation in a prostate cancer cell line. In mice, MJM-1 injected intraperitoneally (i.p.) crossed the BBB and could be detected in the hippocampus, a brain region that mediates memory. Consistent with this finding, we found that the post-training i.p. administration of MJM-1 enhanced hippocampus-dependent spatial memory consolidation in male mice. Therefore, MJM-1 represents a potential lead for further optimization as a therapeutic strategy for ameliorating cognitive deficits in aging and neurodegenerative diseases.

Indexed as

AnimalsBrainCell Line, TumorHistone Deacetylase InhibitorsMiceMice, Inbred BALB CSpatial MemoryHistone Deacetylase Inhibitors

Identifiers

PMID35133171
PMCPMC9135144

What OpenQuestion holds

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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.