Evidence map›Paper›PMID 37862143›Full record

ArticleJournal of medicinal chemistry2023

First Optimization of Novel, Potent, Selective PDE11A4 Inhibitors for Age-Related Cognitive Decline.

Shams Ul Mahmood, Mariana Lozano Gonzalez, Sreedhar Tummalapalli, Jeremy Eberhard, Judy Ly, Charles S Hoffman, Michy P Kelly, John Gordon, Dennis Colussi, Wayne Childers and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. First Demonstration ofJournal of medicinal chemistry · 2024
    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

11 authors at 4 institutions in 1 country.

Shams Ul MahmoodDepartment of Chemistry & Biochemistry, Montclair State University, Montclair, New Jersey 07043, United States.
Mariana Lozano GonzalezDepartment of Chemistry & Biochemistry, Montclair State University, Montclair, New Jersey 07043, United States.
Sreedhar TummalapalliDepartment of Chemistry & Biochemistry, Montclair State University, Montclair, New Jersey 07043, United States.
Jeremy EberhardBiology Department, Boston College, Chestnut Hill, Massachusetts 02467, United States.
Judy LyBiology Department, Boston College, Chestnut Hill, Massachusetts 02467, United States.
Charles S HoffmanBiology Department, Boston College, Chestnut Hill, Massachusetts 02467, United States.
Michy P KellyDepartment of Anatomy & Neurobiology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, United States.
John GordonMoulder Center for Drug Discovery Research, Temple University, Philadelphia, Pennsylvania 19140, United States.
Dennis ColussiMoulder Center for Drug Discovery Research, Temple University, Philadelphia, Pennsylvania 19140, United States.
Wayne ChildersMoulder Center for Drug Discovery Research, Temple University, Philadelphia, Pennsylvania 19140, United States.
David P RotellaDepartment of Chemistry & Biochemistry, Montclair State University, Montclair, New Jersey 07043, United States.ORCID 0000-0002-8224-218X
Montclair State University · USBoston College · USTemple University · USUniversity of Maryland, Baltimore · US

Funding

Pharmacologic Inhibition of PDE11A for Age-Related Memory DisordersR01AG067836 · NIA · MONTCLAIR STATE UNIVERSITY · PI HOFFMAN, CHARLES S., KELLY, MICHY PATRICE · 2020 to 2024
$3.6M
NIA NIH HHS R01 AG067836
6 · The paper itself

Abstract

Phosphodiesterase 11A4 (PDE11A4) is a dual-acting cyclic nucleotide hydrolase expressed in neurons in the CA1, subiculum, amygdalostriatal transition area and amygdalohippocampal area of the extended hippocampal formation. PDE11A4 is the only PDE enzyme to emanate solely from hippocampal formation, a key brain region for the formation of long-term memory. PDE11A4 expression increases in the hippocampal formation of both humans and rodents as they age. Interestingly, PDE11A knockout mice do not show age-related deficits in associative memory and show no gross histopathology. This suggests that inhibition of PDE11A4 might serve as a therapeutic option for age-related cognitive decline. A novel, yeast-based high throughput screen previously identified moderately potent, selective PDE11A4 inhibitors, and this work describes initial efforts that improved potency more than 10-fold and improved some pharmaceutical properties of one of these scaffolds, leading to selective, cell-penetrant PDE11A4 inhibitors, one of which is 10-fold more potent compared to tadalafil in cell-based activity.

Indexed as

3',5'-Cyclic-GMP PhosphodiesterasesCognitive DysfunctionPhosphodiesterase InhibitorsAnimalsBrainHumansMiceMice, KnockoutPhosphoric Diester Hydrolases3',5'-Cyclic-GMP PhosphodiesterasesPDE11A protein, humanPde11a protein, mousePhosphodiesterase InhibitorsPhosphoric Diester Hydrolases

Identifiers

PMID37862143
PMCPMC10641827
OpenAlexW4387823058

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.