ArticleJournal of medicinal chemistry2021
Generation of Highly Selective, Potent, and Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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.
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.
Who cites it
9 citing papers in PubMed.
- Understanding how a highly prevalent GRK5 polymorphism affects platelets and enhances thrombotic risk.Blood · 2026Article
- Revealing GRK5 Activation Features by Interpretable Machine Learning and Molecular Dynamics Simulation.International journal of molecular sciences · 2026Article
- Cell-based and isoform-selective G protein-coupled receptor kinase assays for comprehensive inhibitor evaluation.Communications biology · 2026Article
- High-Throughput Cardiac Hypertrophy Phenotyping Supports Lead Optimization of GRK5 Inhibitors.ACS medicinal chemistry letters · 2026Article
- Potent, Selective, and Drug-Like G Protein-Coupled Receptor Kinase 5 and 6 Inhibitors: Design, Synthesis, and X-Ray Structural Studies.ChemMedChem · 2025Article
- Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators.iScience · 2025Article
- Design, synthesis, and X-ray structural studies of a series of highly potent, selective, and drug-like G protein-coupled receptor kinase 5 inhibitors.European journal of medicinal chemistry · 2025Article
- Development of a new class of potent and highly selective G protein-coupled receptor kinase 5 inhibitors and structural insight from crystal structures of inhibitor complexes.European journal of medicinal chemistry · 2024Article
- A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening.Communications biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
The ability of G protein-coupled receptor (GPCR) kinases (GRKs) to regulate the desensitization of GPCRs has made GRK2 and GRK5 attractive targets for treating diseases such as heart failure and cancer. Previously, our work showed that Cys474, a GRK5 subfamily-specific residue located on a flexible loop adjacent to the active site, can be used as a covalent handle to achieve selective inhibition of GRK5 over GRK2 subfamily members. However, the potency of the most selective inhibitors remained modest. Herein, we describe a successful campaign to adapt an indolinone scaffold with covalent warheads, resulting in a series of 2-haloacetyl-containing compounds that react quickly and exhibit three orders of magnitude selectivity for GRK5 over GRK2 and low nanomolar potency. They however retain a similar selectivity profile across the kinome as the core scaffold, which was based on Sunitinib.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.