GRK

CCG215022 is a potent GRK2 and GRK5 inhibitor. CCG215022 exhibited nanomolar IC50 values against both GRK2 and GRK5 and good selectivity against other closely related kinases such as GRK1 and PKA.

CMPD101, is a novel membrane-permeable, small-molecule inhibitor of both GRK2 and GRK3 with IC50s of 18 nM and 5.4 nM. CMPD101 also inhibits ROCK-2 and PKCα (IC50s=1.4 μM and 8.1 μM, respectively).

GRKs-IN-1, Compound 14as, has remarkable potency against and selectivity for G protein-coupled receptor kinase 2 GRK2 (IC50=30 nM) and GRK5 (IC50=7.1 μM). GRKs-IN-1 is a derivative 14as of paroxetine, shows a 100-fold improvement in cardiomyocyte contractility assays over paroxetine.

GSK180736A is a G protein-coupled receptor kinase 2 (GRK2) inhibitor with an IC50 of 0.77 μM.

Takeda103A is a potent GRK2-dependent bovine tubulin oxidation inhibitor.

KR-39038 is a potent and orally bioavailable inhibitor of G protein-coupled receptor kinase 5 (GRK5), with an IC₅₀ of 0.02 μM. It effectively suppresses angiotensin II–induced cellular hypertrophy by inhibiting the HDAC5 signaling pathway in neonatal cardiomyocytes. KR-39038 exhibits strong anti-hypertrophic activity and improves cardiac function in preclinical models, making it a promising candidate for research in heart failure and related cardiovascular diseases.

GRK2 degrader-1 is a potent and orally active degrader of G protein-coupled receptor kinase 2 (GRK2) that mediates its degradation through the ubiquitin-proteasome pathway. This compound effectively inhibits right ventricular remodeling and reduces pulmonary artery pressure in mouse models of pulmonary artery hypertension (PAH). GRK2 degrader-1 serves as a valuable tool for investigating the role of GRK2 in PAH and related cardiovascular research.

CCG 224061 is a selective inhibitor of G protein-coupled receptor kinase 2 (GRK2) with an IC50 of 0.066 μM. It effectively inhibits GRK activity in cardiomyocytes, making it a valuable tool for studying cardiac signaling pathways. This compound is particularly relevant for research focused on heart disease, heart failure, myocardial hypertrophy, and hypertension.

CCG273441 is a selective covalent inhibitor of G protein-coupled receptor kinase 5 (GRK5), exhibiting an IC50 value of 3.8 nM. This compound demonstrates a high degree of selectivity over GRK2, with an IC50 of 4.8 μM, by targeting and covalently binding to the Cys474 residue, which is unique to the GRK5 subfamily. CCG273441 serves as a valuable tool for research into GRK5-related signaling pathways and potential therapeutic applications in various disease models.

CCG258747 is a potent and selective inhibitor of GRK2, demonstrating an IC50 value of 18 nM and high selectivity against GRK1, GRK5, PKA, and ROCK1. This compound effectively prevents the internalization of the µ-opioid receptor (MOR) and inhibits the IgE-mediated anaphylaxis via the GRK2 and FcεRI signaling pathway, while also activating mast cells through MRGPRX2 and MRGPRB2. CCG258747 serves as a valuable tool for investigating disease mechanisms associated with GRK2 overexpression, including heart failure and opioid tolerance.

Rovunaptabin (ARC 183) is an aptamer consisting of a single-stranded DNA molecule made up of 15 deoxynucleotides, specifically designed to neutralize pathogenic G-protein-coupled receptor autoantibodies. It exhibits broad-spectrum activity, making it a valuable tool for studying diseases such as cardiomyopathy and pulmonary hypertension. Researchers can utilize Rovunaptabin to investigate the underlying mechanisms and potential therapeutic approaches related to these conditions.

GRK-IN-1 is a selective inhibitor of G protein-coupled receptor kinases (GRKs), which play a crucial role in the regulation of receptor desensitization and downregulation. This compound exhibits potential biological activity in modulating signaling pathways mediated by GPCRs, making it valuable for research focused on cardiovascular diseases, neurological disorders, and cancer. GRK-IN-1 can be utilized to investigate the impact of GRK inhibition on cellular signaling and to explore therapeutic strategies targeting GRK-related pathways.

GRK6-IN-3 is a selective inhibitor of G protein-coupled receptor kinase 6 (GRK6), exhibiting an IC50 value of 1.03 μM. This compound modulates GRK6 activity, which is crucial for various cellular signaling pathways. GRK6-IN-3 is suitable for research applications aimed at exploring GRK6's role in receptor desensitization and its implications in various physiological and pathological processes.

CCG-271423 is a selective inhibitor of G protein-coupled receptor kinase 5 (GRK5), demonstrating an IC50 of 2.1 nM for GRK5 and 44 μM for GRK2. This compound effectively reduces cardiomyocyte contractility and lowers calcium transient levels, making it valuable for cardiac research. Additionally, CCG-271423 features an alkyne group, enabling its use in copper-catalyzed azide-alkyne cycloaddition (CuAAc) for bioconjugation applications.

GRK5-IN-4 is a selective covalent inhibitor of G protein-coupled receptor kinase 5 (GRK5), exhibiting an IC50 of 1.1 μM and demonstrating 90-fold selectivity over GRK2. This compound serves as a valuable tool for heart failure research by modulating GRK5 activity. Additionally, GRK5-IN-4 features an alkyne group, enabling it to participate in copper-catalyzed azide-alkyne cycloaddition (CuAAc) reactions, making it useful for various chemical biology applications.

GRK6-IN-4 is a selective inhibitor of G protein-coupled receptor kinase 6 (GRK6), exhibiting an IC50 of 1.56 μM. This compound plays a crucial role in the modulation of G protein-coupled receptor signaling pathways and is relevant for research investigating hematological malignancies, inflammatory diseases, and autoimmune disorders. By inhibiting GRK6, GRK6-IN-4 provides valuable insights into the underlying mechanisms of these conditions and potential therapeutic strategies.

CCG 258001 is a selective inhibitor of G protein-coupled receptor kinases (GRK), demonstrating IC50 values of 0.29 µM for GRK2, 51.8 µM for GRK1, and 33 µM for GRK5. It effectively inhibits GRK activity in cardiomyocytes and other muscle cell types, making it a valuable tool for investigating the role of GRKs in cardiac function. This compound is relevant for research into various cardiovascular conditions, including heart failure, myocardial hypertrophy, and hypertension.

GRL093-22 is a potent and selective inhibitor of G protein-coupled receptor kinases (GRKs), displaying IC50 values of 60 nM for GRK5 and 40 nM for GRK6. This compound is valuable for research on mechanisms underlying heart failure and multiple myeloma, facilitating investigations into the modulation of GRK activity in these conditions.

GRK2i is a selective Gβγ antagonist that inhibits Gβγ-mediated signaling pathways. This peptide corresponds to the Gβγ-binding domain of G-protein-coupled receptor kinase 2 (GRK2), making it a valuable tool for studying G-protein signaling mechanisms. Its application includes investigating the role of Gβγ subunits in various cellular processes and identifying potential therapeutic targets related to G-protein-coupled receptor signaling.

CCG-273463 is a selective covalent inhibitor of G protein-coupled receptor kinase 5 (GRK5), demonstrating an IC50 of 8.6 nM. This compound is instrumental in research related to heart failure, hypertrophic cardiomyopathy, and various cancer pathways. Its specificity for GRK5 makes it a valuable tool for elucidating the role of this kinase in disease mechanisms and therapeutic development.

CCG-224406 is a selective inhibitor of G protein-coupled receptor kinase 2 (GRK2), exhibiting an IC50 of 13 nM and demonstrating over 700-fold selectivity against other GRK subfamilies, with no inhibition of ROCK1. This small molecule is suitable for research into GRK2's role in heart failure and offers a valuable tool for exploring GRK-related signaling pathways in cardiovascular biology.

GRK5-IN-3 is a covalent inhibitor targeting G Protein-Coupled Receptor Kinase 5 (GRK5). This compound demonstrates potent inhibitory activity against GRK5 and GRK6, with IC50 values of 0.22 μM and 0.41 μM, respectively. GRK5-IN-3 is suitable for research applications focused on understanding the role of GRK5 in cellular signaling and its implications in various pathological conditions.

GRK6-IN-5 is a selective inhibitor of G protein-coupled receptor kinase 6 (GRK6), exhibiting an IC50 of 4.48 μM. This compound is instrumental for investigating its role in hematological malignancies, inflammation-related conditions, and autoimmune disorders. Researchers can utilize GRK6-IN-5 to elucidate the biochemical pathways influenced by GRK6, potentially leading to therapeutic advancements in these diseases.

GRK5-IN-5 is a selective inhibitor of G protein-coupled receptor kinase 5 (GRK5), demonstrating an IC50 of 0.03 μM. This compound also exhibits activity against GRK2 and GRK6, with IC50 values of 2.2 μM and 0.036 μM, respectively. GRK5-IN-5 is known for its potent activity in inhibiting myocardial hypertrophy and reducing non-myocardial cell proliferation. It effectively suppresses the upregulation of hypertrophy markers Nppa and Nppb, thereby preventing pathological remodeling of cardiac tissue. This reagent is valuable for investigating mechanisms underlying cardiac hypertrophy.