Evidence map›Paper›PMID 39321314›Full record

ArticleJournal of medicinal chemistry2024

First Demonstration of

Shams Ul Mahmood, Jeremy Eberhard, Charles S Hoffman, Dennis Colussi, John Gordon, Wayne Childers, Elvis Amurrio, Janvi Patel, Michy P Kelly, David P Rotella

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2024. 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. Article
  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

10 authors.

Shams Ul MahmoodDepartment of Chemistry and Biochemistry, Montclair State University, 1 Normal Avenue, Montclair, New Jersey 07043, United States.
Jeremy EberhardBiology Department, Boston College, Chestnut Hill, Massachusetts 02467, United States.
Charles S HoffmanBiology Department, Boston College, Chestnut Hill, Massachusetts 02467, United States.ORCID 0000-0001-8700-1863
Dennis ColussiMoulder Center for Drug Discovery Research, Temple University, Philadelphia, Pennsylvania 19140, United States.
John GordonMoulder 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.
Elvis AmurrioDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
Janvi PatelDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
Michy P KellyDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States.
David P RotellaDepartment of Chemistry and Biochemistry, Montclair State University, 1 Normal Avenue, Montclair, New Jersey 07043, United States.ORCID 0000-0002-8224-218X

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

PDE11A4 is a target of interest for the treatment of age-related memory disorders. A previous report from our laboratories described an amide series of potent, selective PDE11A4 inhibitors that was metabolically unstable. Investigation of heterocyclic amide isosteres for the labile amide moiety revealed distinct structure-activity relationships and identified several compounds with potency comparable to the amide series. This manuscript describes the characterization of structure-activity and structure-property relationships in this set, leading to the identification of an orally bioavailable, brain-penetrant, selective and potent PDE11A4 inhibitor. Target engagement experiments demonstrated PDE11A4 inhibition in the hypothalamus of mice that was absent in PDE11A4 knock out animals.

Indexed as

3',5'-Cyclic-AMP PhosphodiesterasesMemory DisordersPhosphodiesterase Inhibitors3',5'-Cyclic-GMP PhosphodiesterasesAgingAnimalsHumansHypothalamusMaleMiceMice, KnockoutStructure-Activity Relationship3',5'-Cyclic-AMP Phosphodiesterases3',5'-Cyclic-GMP PhosphodiesterasesPde11a protein, mousePhosphodiesterase Inhibitors

Identifiers

PMID39321314
PMCPMC11472338

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.