Evidence map›Paper›PMID 40238995›Full record

ArticleChemMedChem2025

Further Structure-Activity Relationship of G Protein-Gated Inwardly Rectifying Potassium Channels 1/2 Activators: Synthesis and Biological Characterization of In Vitro Tool Compounds.

Sumaiya Nahid, Fahad Imtiaz Rahman, Yu Du, Brittany D Spitznagel, Sandeep K Singh, Yashpal S Chhonker, Daryl J Murry, C David Weaver, Corey R Hopkins

Abstract read
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In one paragraph

Article in ChemMedChem, 2025. 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
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0citing papers in PubMed
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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.

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

9 authors.

Sumaiya NahidDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Fahad Imtiaz RahmanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Yu DuDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Brittany D SpitznagelDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Sandeep K SinghDepartment of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Yashpal S ChhonkerDepartment of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Daryl J MurryDepartment of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
C David WeaverDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Corey R HopkinsDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.ORCID https://orcid.org/0000-0003-4958-1697

Funding

Discovery and characterization of selective GIRK1/2 activators and their evaluation in preclinical models of painR01NS127439 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Jerod S. Denton, Corey R. Hopkins · 2022 to 2026
$2.2M
NINDS NIH HHS R01 NS127439NINDS NIH HHS R01NS127439
6 · The paper itself

Abstract

The work presented herein outlines the ongoing structure-activity relationship studies centered around a potent, efficacious, and selective activators of the G protein-gated inwardly rectifying potassium channels (GIRK)1/2 channel. Optimization studies centered around the pyrazole privileged scaffold, the N-1-position of the pyrazole, and the right-hand ether. The work confirms the necessity of the pyrazole, and a more potent GIRK1/2 activator is identified with ≈12-fold selectivity against GIRK1/4. The metabolite ID study is reported which shows the instability of the amide bond as the major site of metabolism (nonNADPH mediated). This work discovers another highly potent and selective GIRK1/2 activator for use as an in vitro tool compound.

Indexed as

G Protein-Coupled Inwardly-Rectifying Potassium ChannelsPyrazolesAnimalsDose-Response Relationship, DrugHumansMolecular StructureStructure-Activity RelationshipG Protein-Coupled Inwardly-Rectifying Potassium ChannelsPyrazolesactivatorG protein‐gated inwardly rectifying potassium channelsmetabolite IDstructure‐activity relationship

Identifiers

PMID40238995
PMCPMC12221119

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Registered trials

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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.