Evidence map›Paper›PMID 34413956›Full record

ArticleACS medicinal chemistry letters2021

Discovery of the First Non-cGMP Mimetic Small Molecule Activators of cGMP-Dependent Protein Kinase 1 α (PKG1α).

Jennifer Hanisak, Aileen Soriano, Gregory C Adam, Andrea Basso, David Bauman, David Bell, Emily Frank, Gregory O'Donnell, Paul Tawa, Andreas Verras and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

13 authors.

Jennifer HanisakDiscovery Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Aileen SorianoMass Spectrometry and Biophysics, Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Gregory C AdamQuantitative Biosciences, Merck & Co., Inc, West Point, Pennsylvania 19486, United States.
Andrea BassoMass Spectrometry and Biophysics, Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
David BaumanDiscovery Biology, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
David BellMass Spectrometry and Biophysics, Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Emily FrankMass Spectrometry and Biophysics, Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Gregory O'DonnellQuantitative Biosciences, Merck & Co., Inc, West Point, Pennsylvania 19486, United States.
Paul TawaMass Spectrometry and Biophysics, Computational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Andreas VerrasComputational and Structural Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Yang YuDiscovery Chemistry, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
Lei ZhangBiologics Analytical Research and Development, Merck & Co., Inc., Kenilworth, New Jersey, 07033 United States.
W Michael SeganishDiscovery Chemistry, Merck & Co., Inc., South San Francisco, California 94080, United States.ORCID https://orcid.org/0000-0001-6605-2856

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PKG1α is a central node in cGMP signaling. Current therapeutics that look to activate this pathway rely on elevation of cGMP levels and subsequent activation of PKG1α. Direct activation of PKG1α could potentially drive additional efficacy without associated side effects of blanket cGMP elevation. We undertook a high-throughput screen to identify novel activators. After triaging through numerous false positive hits, attributed to compound mediated oxidation and activation of PKG1α, a piperidine series of compounds was validated. The hit

Identifiers

PMID34413956
PMCPMC8365999

What OpenQuestion holds

Textmetadata
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.