2. Signaling Pathways
  3. GPCR/G Protein
  4. G Protein-coupled Receptor Kinase (GRK)

G Protein-coupled Receptor Kinase (GRK)

G protein-coupled receptor kinases (GRKs) are a family of serine/threonine kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. On the basis of their sequence homology, GRKs can be subclassified into three groups: the visual subfamily (GRK1 and GRK7), the GRK4 subfamily (GRK4, GRK5 and GRK6) and the β-AR kinase (βARK) subfamily (GRK2 and GRK3). GRK1 and GRK7 are primarily expressed in retinal photoreceptor cells, whereas GRK4 is most abundantly expressed in the testes. GRK2, GRK3 and GRK5 are ubiquitously expressed, albeit to various extents in different tissues. In the heart, GRK2 and GRK5 are most prominent, whereas GRK3 and GRK6 are expressed at low levels. Functionally, all GRKs mediate the uncoupling and internalization of activated GPCRs. All GRKs are primarily localized to the cytosol and plasma membrane. GRK1, GRK4, GRK5, GRK6 and GRK7 are basally localized to the membrane. Conversely, GRK2 and GRK3 are primarily localized to the cytosol and translocate to the membrane after receptor stimulation.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-142812
    GRK6-IN-1
    		99.64%
    GRK6-IN-1 (compound 18) is a potent inhibitor of G protein-coupled receptor kinase 6 (GRK6) with an IC50 of 120 nM. GRK6 is a critical kinase required for the survival of multiple myeloma (MM) cells. GRK6-IN-1 has the potential for the research of multiple myeloma.
    GRK6-IN-1
  • HY-136561
    GRK5-IN-2
    		99.92%
    GRK5-IN-2 (compound 707), a pyridine-based bicyclic compound, is a potent G-protein-coupled receptor kinase 5 (GRK5) inhibitor. GRK5-IN-2 regulates the expression and/or release of insulin and is useful for the metabolic disease research.
    GRK5-IN-2
  • HY-109562A
    CCG258208 hydrochloride
    		98.05%
    CCG258208 (GRK2-IN-1) hydrochloride is a potent and selective GRK2 (G protein-coupled receptor kinase 2) inhibitor (IC50=30 nM) while maintaining 230-fold selectivity over GRK5 (IC50=7.09 μM) and more than 2500-fold selectivity over GRK1 (IC50=87.3 μM), PKA, and ROCK1. CCG258208 hydrochloride can be used in heart failure research.
    CCG258208 hydrochloride
  • HY-142817
    GRK6-IN-2
    		99.39%
    GRK6-IN-2 (compound 10a) is a potent inhibitor of G protein-coupled receptor kinase 6 (GRK6) with an IC50 of 120 nM. GRK6 is a critical kinase required for the survival of multiple myeloma (MM) cells. GRK6-IN-2 has the potential for the research of multiple myeloma.
    GRK6-IN-2
  • HY-47573
    CCG273441
    		Inhibitor 98.67%
    CCG273441 is a covalent inhibitor of G protein-coupled receptor (GPCR) kinase 5 (GRK5) with an IC50 value of 3.8 nM. CCG273441 is highly selective to GRK5 over GRK2 (IC50=4.8 μM) by binding Cys474, a GRK5 subfamily-specific residue, as a covalent handle.
    CCG273441
  • HY-123862
    LAS195319
    		Inhibitor
    LAS195319 is an orally active and potent inhibitor against PI3Kδ with an IC50 value of 0.5 nM. LAS195319 is also a highly selective inhibitor against an extensive panel of proteins, lipid kinases and GPCRs. LAS195319 causes an inhibition of neutrophil and eosinophil infiltration. LAS195319 is promising for research of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
    LAS195319
  • HY-118046
    GSK2163632A
    		Inhibitor
    GSK2163632A is a selective G protein-coupled receptor kinase (GRK) inhibitor that may serve as a probe for studying heart failure and Parkinson's disease. Screening of known protein kinase inhibitors by differential scanning fluorescence method revealed that the melting points of GRK2 and GRK5 increased. Enzymatic assays of the 14 most stable hits revealed that three exhibited nanomolar inhibitory potency against a single GRK, with some showing significant selectivity. Most of the identified compounds can be divided into two categories: indazole/dihydropyrimidine compounds selectively inhibit GRK2, and pyrrolopyrimidine compounds effectively inhibit GRK1 and GRK5 but with modest selectivity. The two most inhibitory representative compounds, GSK180736A and GSK2163632A, are co-crystals with GRK2 and GRK1, respectively, and their atomic structures were determined to 2.6 and 1.85 ? distances, respectively. GSK180736A, as an inhibitor of Rho-related coiled-coil protein kinase, binds to GRK2 in a manner similar to paroxetine, while GSK2163632A, as an inhibitor of insulin-like growth factor 1 receptor, occupies a novel region of the GRK active site cleft and may be used to achieve more Selectivity. However, both compounds inhibited GRK no more potently than their original targets. These data provide a basis for the rational design of more effective and selective GRK inhibitors in the future.
    GSK2163632A
  • HY-159972
    PKR1 antagonist 1
    		Antagonist
    PKR1 antagonist 1 (PC1) is a potent PKR1 antagonist. PKR1 antagonist 1 reduces hyperalgesia and allodynia in SNI mice.
    PKR1 antagonist 1
  • HY-143248
    KR-39038
    		Inhibitor 99.48%
    KR-39038 is an orally active and potent GRK5 (G protein-coupled receptor kinase 5) inhibitor, with an IC50 of 0.02 μM. KR-39038 significantly inhibits angiotensin II-induced cellular hypertrophy through suppression of HDAC5 pathway in neonatal cardiomyocytes. KR-39038 shows profound anti-hypertrophic effects and improved cardiac function. KR-39038 can be used for heart failure research.
    KR-39038
  • HY-156863
    GRK2 Inhibitor 2
    		Inhibitor 98.88%
    GRK2 Inhibitor 2 (Compound 8h) is a GRK2 inhibitor (IC50: 19 nM). GRK2 Inhibitor 2 also inhibits Aurora-A (IC50: 137 nM). GRK2 Inhibitor 2 promotes β-AR-mediated cAMP accumulation in GRK2-overexpressed HEK293 cells. GRK2 Inhibitor 2 can be used for research of congestive heart failure (HF).
    GRK2 Inhibitor 2
  • HY-P1396A
    GRK2i TFA
    		Inhibitor 98.41%
    GRK2i TFA is a GRK2 inhibitory polypeptide that specifically inhibits Gβγ activation of GRK2. GRK2i TFA corresponds to the Gβγ-binding domain and acts as a cellular Gβγ antagonist.
    GRK2i TFA
  • HY-149720
    GRL018-21
    		Inhibitor
    GRL018-21 is a potent and highly selective G protein-coupled receptor kinase 5 (GRK5) inhibitor with an IC50 value of 10 nM.
    GRL018-21
  • HY-109562
    CCG258208
    CCG258208 (GRK2-IN-1) is a potent and selective GRK2 (G protein-coupled receptor kinase 2) inhibitor (IC50=30 nM) while maintaining 230-fold selectivity over GRK5 (IC50=7.09 μM) and more than 2500-fold selectivity over GRK1 (IC50=87.3 μM), PKA, and ROCK1. CCG258208 can be used in heart failure research.
    CCG258208
  • HY-128311
    GRK6-IN-3
    		Inhibitor
    GRK6-IN-3 is a G protein coupled receptor 6 kinase (GRK6) inhibitor with an IC50 1.03 μM.
    GRK6-IN-3
  • HY-P3035
    Corazonin
    Corazonin is a highly conserved neuropeptide hormone of wide-spread occurrence in insects, serves a central regulator of caste identity and behavior in social insects. Corazonin is also preferentially expressed in workers and/or foragers from other social insect species.
    Corazonin
  • HY-111239
    GSK317354A
    		Inhibitor
    GSK317354A is a ROCK and GRK inhibitor. GSK317354A can be used for heart failure and Parkinson’s disease research.
    GSK317354A
  • HY-150039
    CCG-271423
    		Inhibitor
    CCG-271423 is a potent and selective GRK5 inhibitor with IC50 values of 0.0021 μM and 44 μM for GRK5 and GRK2, respectively. CCG-271423 inhibits cardiomyocyte contractility and decreases in Ca2+ transience. CCG-271423 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    CCG-271423
  • HY-150022
    GRK5-IN-4
    		Inhibitor
    GRK5-IN-4 (Compound 16d, CCG-265328) is a potent and and selective covalent GRK5 (G protein-coupled receptor kinase 5) inhibitor, with an IC50 of 1.1 μM. GRK5-IN-4 shows 90-fold selectivity over GRK2. GRK5-IN-4 can be used for heart failure research. GRK5-IN-4 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
    GRK5-IN-4
  • HY-123520
    GSK299115A
    		Inhibitor
    GSK299115A is a G Protein-coupled Receptor Kinase (GRK) and PKA inhibitor.
    GSK299115A
  • HY-P1396
    GRK2i
    		Inhibitor
    GRK2i is a Gβγ-inhibitory peptide that selectively prevents Gβγ-mediated signaling. GRK2i corresponds to the Gβγ-binding domain of GRK2 (G-protein-coupled receptor kinase 2).
    GRK2i
Cat. No. Product Name / Synonyms Application Reactivity