ArticleJournal of medicinal chemistry2016
Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- Canonical or non-canonical, all aspects of G protein-coupled receptor kinase 2 in heart failure.Acta physiologica (Oxford, England) · 2025Review
- Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics.Mediators of inflammation · 2025Review
- GRK2 mediates cisplatin-induced acute liver injury via the modulation of NOX4.Cell biology and toxicology · 2024Article
- Control of GαScience advances · 2022Article
- Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats.Acta pharmaceutica Sinica. B · 2021Article
- Article
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- Synthesis, crystal structure and antibacterial studies of dihydropyrimidines and their regioselectively oxidized products.RSC advances · 2021Article
- A New Paroxetine-Based GRK2 Inhibitor Reduces Internalization of theMolecular pharmacology · 2020Article
- Characterization of a hyperphosphorylated variant of G protein-coupled receptor kinase 5 expressed in E. coli.Protein expression and purification · 2020Article
- Structure-Based Design of Selective, Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.ACS medicinal chemistry letters · 2019Article
- Multi-functionality of proteins involved in GPCR and G protein signaling: making sense of structure-function continuum with intrinsic disorder-based proteoforms.Cellular and molecular life sciences : CMLS · 2019Review
- G protein-coupled receptor kinases as therapeutic targets in the heart.Nature reviews. Cardiology · 2019Review
- GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis.Scientific reports · 2019Article
- Computational study of paroxetine-like inhibitors reveals new molecular insight to inhibit GRK2 with selectivity over ROCK1.Scientific reports · 2019Article
- Perturbation of the interactions of calmodulin with GRK5 using a natural product chemical probe.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- G Protein-Coupled Receptor Kinase 2 (GRK2) as a Potential Therapeutic Target in Cardiovascular and Metabolic Diseases.Frontiers in pharmacology · 2019Review
- Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives.Molecules (Basel, Switzerland) · 2018Review
- Small-Molecule G Protein-Coupled Receptor Kinase Inhibitors Attenuate G Protein-Coupled Receptor Kinase 2-Mediated Desensitization of Vasoconstrictor-Induced Arterial Contractions.Molecular pharmacology · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) are central to many physiological processes. Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failure. GSK180736A, developed as a Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site. Guided by its binding pose overlaid with the binding pose of a known potent GRK2 inhibitor, Takeda103A, a library of hybrid inhibitors was developed. This campaign produced several compounds possessing high potency and selectivity for GRK2 over other GRK subfamilies, PKA, and ROCK1. The most selective compound, 12n (CCG-224406), had an IC50 for GRK2 of 130 nM, >700-fold selectivity over other GRK subfamilies, and no detectable inhibition of ROCK1. Four of the new inhibitors were crystallized with GRK2 to give molecular insights into the binding and kinase selectivity of this class of inhibitors.
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Registered trials
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.