Evidence map›Paper›PMID 29627263›Full record

ArticleBioorganic & medicinal chemistry letters2018

Utilizing a structure-based docking approach to develop potent G protein-coupled receptor kinase (GRK) 2 and 5 inhibitors.

Helen V Waldschmidt, Renee Bouley, Paul D Kirchhoff, Pil Lee, John J G Tesmer, Scott D Larsen

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
    Review
  3. Article
  4. Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021
    Article
  5. Article
  6. Article
  7. Review
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

6 authors at 1 institution in 1 country.

Helen V WaldschmidtDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States; Vahlteich Medicinal Chemistry Core, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
Renee BouleyDepartment of Pharmacology and the Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States.
Paul D KirchhoffVahlteich Medicinal Chemistry Core, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
Pil LeeVahlteich Medicinal Chemistry Core, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
John J G TesmerDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States; Department of Pharmacology and the Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States; Department of Biological Sciences, Purdue University, West Lafayette, IN, United States.
Scott D LarsenDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States; Vahlteich Medicinal Chemistry Core, College of Pharmacy, University of Michigan, Ann Arbor, MI, United States. Electronic address: sdlarsen@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Structure, function, and inhibition of G protein-coupled receptor kinasesR01HL071818 · NHLBI · UNIVERSITY OF TEXAS AUSTIN · PI TESMER, JOHN · 2004 to 2023
$7.1M
Structure and Function of the LPLA2/LCAT Acyltransferase FamilyR01HL122416 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESMER, JOHN · 2015 to 2018
$1.9M
NHLBI NIH HHS R01 HL071818NHLBI NIH HHS R01 HL122416
6 · The paper itself

Abstract

G protein-coupled receptor (GPCR) kinases (GRKs) regulate the desensitization and internalization of GPCRs. Two of these, GRK2 and GRK5, are upregulated in heart failure and are promising targets for heart failure treatment. Although there have been several reports of potent and selective inhibitors of GRK2 there are few for GRK5. Herein, we describe a ligand docking approach utilizing the crystal structures of the GRK2-Gβγ·GSK180736A and GRK5·CCG215022 complexes to search for amide substituents predicted to confer GRK2 and/or GRK5 potency and selectivity. From this campaign, we successfully generated two new potent GRK5 inhibitors, although neither exhibited selectivity over GRK2.

Indexed as

Molecular Docking SimulationAmidesDose-Response Relationship, DrugG-Protein-Coupled Receptor Kinase 2G-Protein-Coupled Receptor Kinase 5HumansMolecular StructureProtein Kinase InhibitorsStructure-Activity RelationshipAmidesG-Protein-Coupled Receptor Kinase 2G-Protein-Coupled Receptor Kinase 5GRK2 protein, humanGRK5 protein, humanProtein Kinase InhibitorsCrystallographyDockingGPCRsGRKsKinases

Identifiers

PMID29627263
PMCPMC5916850
OpenAlexW2794937437

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.