Evidence map›Paper›PMID 39116711›Full record

ArticleBioorganic & medicinal chemistry2024

Synthesis and biological studies of 2-aminothiophene derivatives as positive allosteric modulators of glucagon-like peptide 1 receptor.

Jeffrey A Campbell, Phu Do, Zhiyu Li, Faisal Malik, Christopher Mead, Nick Miller, Christopher Pisiechko, Kimberly Powers, Zhijun Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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.

Jeffrey A CampbellDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Phu DoDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Zhiyu LiDepartment of Pharmaceutical Sciences, Saint Joseph's University, Philadelphia, PA 19104, USA.
Faisal MalikDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Christopher MeadDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Nick MillerDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Christopher PisiechkoDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Kimberly PowersDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA.
Zhijun LiDepartment of Chemistry and Biochemistry, Saint Joseph's University, Philadelphia, PA 19104, USA. Electronic address: zli1@sju.edu.

Funding

Is there a common allosteric binding site for all GPCRs?R15GM140406 · NIGMS · UNIVERSITY OF THE SCIENCES PHILADELPHIA · PI LI, ZHIJUN · 2020 to 2022
$531k
NIGMS NIH HHS R15 GM140406
6 · The paper itself

Abstract

As a step toward the development of novel small-molecule positive allosteric modulators (PAMs) of glucagon-like peptide 1 receptor (GLP-1R) for the treatment of type 2 diabetes, obesity, and heart diseases, we discovered a novel 2-amino-thiophene (2-AT) based lead compound bearing an ethyl 3-carboxylate appendage. In this work, we report the syntheses and biological studies of more than forty 2-AT analogs, that have revealed a 2-aminothiophene-3-arylketone analogue 7 (MW 299) showing approximately a 2-fold increase in insulin secretion at 5 μM when combined with the GLP-1 peptide at 10 nM. In vivo studies using CD1 mice at a dose of 10 mg/kg, clearly demonstrated that the blood plasma glucose level was lowered by 50% after 60 min. Co-treatment of 7 with sitagliptin, an inhibitor of GLP-1 degrading enzyme Dipeptidyl Peptidase IV, further confirmed 7 to be an effective PAM of GLP-1R. The small molecular weight and demonstrated allosteric modulating properties of these compound series, show the potential of these scaffolds for future drug development.

Indexed as

Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsThiophenesAllosteric RegulationAnimalsBlood GlucoseDose-Response Relationship, DrugHumansHypoglycemic AgentsInsulinMiceMolecular StructureSitagliptin PhosphateStructure-Activity RelationshipBlood GlucoseGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsInsulinSitagliptin PhosphateThiophenes2-AminothiopheneGlucagon-like peptide 1 receptorInsulin secretionObesity and type-2 diabetesPositive allosteric modulators

Identifiers

PMID39116711
PMCPMC11360446

What Socratic holds

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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 Socratic graph.