GRK2

Summary

GRK2 (G protein-coupled receptor kinase 2, HGNC:289) is a protein-coding gene on chromosome 11q13.2, encoding Beta-adrenergic receptor kinase 1 (P25098). Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them.

This gene encodes a member of the G protein-coupled receptor kinase family of proteins. The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. Data from rodent models supports a role for this gene in embryonic development, heart function and metabolism. Elevated expression of this gene has been observed in human patients with heart failure and Alzheimer’s disease.

Source: NCBI Gene 156 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Jeune syndrome (Moderate, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 49 total — 1 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:289
Approved symbol	GRK2
Name	G protein-coupled receptor kinase 2
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BARK1
Ensembl gene	ENSG00000173020
Ensembl biotype	protein_coding
OMIM	109635
Entrez	156

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 18 protein_coding, 7 retained_intron, 5 protein_coding_CDS_not_defined

ENST00000308595, ENST00000416281, ENST00000524899, ENST00000526285, ENST00000526572, ENST00000527176, ENST00000529738, ENST00000529815, ENST00000530291, ENST00000531390, ENST00000532099, ENST00000532611, ENST00000533077, ENST00000534651, ENST00000900273, ENST00000936739, ENST00000936740, ENST00000936741, ENST00000936742, ENST00000936743, ENST00000936744, ENST00000936745, ENST00000936746, ENST00000951316, ENST00000951317, ENST00000951318, ENST00000951319, ENST00000951320, ENST00000951321, ENST00000951322

RefSeq mRNA: 1 — MANE Select: NM_001619 NM_001619

CCDS: CCDS8156

Canonical transcript exons

ENST00000308595 — 21 exons

Exon	Start	End
ENSE00001186767	67281093	67281184
ENSE00001186774	67280732	67280783
ENSE00001356365	67266473	67266812
ENSE00002193440	67285286	67286556
ENSE00003460359	67284847	67284983
ENSE00003467342	67281650	67281728
ENSE00003488820	67283128	67283228
ENSE00003490076	67281459	67281558
ENSE00003500142	67282271	67282365
ENSE00003505811	67284211	67284373
ENSE00003514906	67282435	67282542
ENSE00003527156	67277272	67277348
ENSE00003567033	67282752	67282818
ENSE00003577547	67283707	67283773
ENSE00003585774	67281822	67281952
ENSE00003585934	67279839	67279900
ENSE00003620531	67279418	67279519
ENSE00003632297	67283854	67283949
ENSE00003636569	67279200	67279273
ENSE00003683305	67285075	67285188
ENSE00003685082	67279626	67279700

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.7317 / max 5250.8079, expressed in 1804 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115413	35.7370	1796
115414	1.3400	472
115410	0.9075	553
206349	0.8973	481
115412	0.7915	416
115426	0.5651	124
115421	0.5560	254
115411	0.4070	176
115422	0.2899	153
115424	0.1714	62

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.09	gold quality
monocyte	CL:0000576	98.31	gold quality
leukocyte	CL:0000738	98.03	gold quality
mononuclear cell	CL:0000842	98.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.75	gold quality
cerebellar hemisphere	UBERON:0002245	97.36	gold quality
spleen	UBERON:0002106	97.23	gold quality
cerebellar cortex	UBERON:0002129	97.17	gold quality
right frontal lobe	UBERON:0002810	97.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.02	gold quality
lower esophagus mucosa	UBERON:0035834	96.79	gold quality
skin of leg	UBERON:0001511	96.69	gold quality
skin of abdomen	UBERON:0001416	96.57	gold quality
upper lobe of left lung	UBERON:0008952	96.31	gold quality
right lung	UBERON:0002167	96.21	gold quality
gall bladder	UBERON:0002110	96.09	gold quality
mucosa of transverse colon	UBERON:0004991	96.09	gold quality
ganglionic eminence	UBERON:0004023	95.98	gold quality
transverse colon	UBERON:0001157	95.89	gold quality
right uterine tube	UBERON:0001302	95.79	gold quality
mucosa of stomach	UBERON:0001199	95.55	gold quality
left uterine tube	UBERON:0001303	95.45	gold quality
colonic epithelium	UBERON:0000397	95.34	gold quality
minor salivary gland	UBERON:0001830	95.34	gold quality
right coronary artery	UBERON:0001625	95.33	gold quality
metanephros cortex	UBERON:0010533	95.30	gold quality
endocervix	UBERON:0000458	95.17	gold quality
cingulate cortex	UBERON:0003027	95.11	gold quality
sural nerve	UBERON:0015488	95.11	gold quality
body of stomach	UBERON:0001161	95.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	24.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

68 targeting GRK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3140-5P	99.39	69.04	1136

Literature-anchored findings (GeneRIF, showing 40)

• GRK2-phosphorylated recombinant ribosomal protein P2 reconstitutes translational activity of 60S ribosomal subunits and represents a potential novel signaling pathway responsible for P2 phosphorylation. (PMID:12379128)
• a direct correlation between the expression of GRK2 and the desensitization of natively expressed H2 receptors in U-937 cells (PMID:12435819)
• GRK2 plays a negative feedback regulatory role on protein kinase C(PKC)beta 1 activity in interaction between GRK2 and PKCbeta 1. (PMID:12456365)
• identification of the amino-terminal domain as a regulatory Gbeta gamma binding site (PMID:12486133)
• GRK2 is potential marker for organ injury and survival after cardiopulmonary bypass (PMID:12552191)
• PDEG functions to link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase by epidermal growth factor (PMID:12624098)
• The pleckstsrin homology domain of this protein binds to PKC and affects the activity of PKC kinase. (PMID:12679936)
• GRK2 requires agonist-induced formation of opioid receptor-G protein-coupled receptor kinase (GRK)-G beta gamma complex on the membrane in order to function (PMID:12750365)
• GRK2 (and also GRK3, GRK5, and GRK6) is stabilized by interaction with Hsp90; GRK2 degradation induced by geldanamycin was predominantly through the proteasome pathway (PMID:14557268)
• The concentration of betaARK1 in lymphocytes is greater in hypertensive individuals with left ventricular hypertrophy than in those without it (PMID:15097244)
• GPRK2-mediated PDGFRbeta seryl phosphorylation plays an important role in desensitizing PDGFRbeta; this desensitization involves GPRK2-mediated phosphorylation of PDGFRbeta Ser(1104), with consequent dissociation of the PDGFRbeta from NHERF (PMID:15271984)
• analysis of the GRK2 binding site of Galphaq (PMID:15471870)
• role in terminating histamine H1 receptor singnaling by the kinase activity and RGS function of GRK2 (PMID:15542600)
• beta-Arrestin 2 and GRK2 are potential mediators of signaling by activated Smoothened (PMID:15618519)
• GRK2 binding is critical not only for alpha2A-adrenergic receptor phosphorylation but also for full activity of the kinase. (PMID:15653687)
• in leukocytes from patients with active relapsing-remitting multiple sclerosis (MS) or with secondary progressive MS, GRK2 levels are significantly reduced (PMID:15778405)
• Ezrin is a novel substrate of GRK2 (PMID:15843435)
• kinase binding to an mGluR1 domain involved in G protein-coupling is essential for the phosphorylation-independent attenuation of signaling by GRK2 (PMID:15870073)
• the uncoupling and endocytosis of 5-HT4R require different GRK2 concentrations and involve distinct molecular events (PMID:15919661)
• Overall, these data suggest that GRK2 has a regulatory role in EGF-induced ERK/MAPK activation. (PMID:16077899)
• GRK2-as5 has a role in membrane trafficking of the mu-opioid receptor (PMID:16081410)
• identification of the protein G-coupled receptor kinase 2 (GRK2), a kinase involved in the desensitization of G protein-coupled receptors (GPCR), as a downstream target and regulator of the TGFbeta-signaling cascade (PMID:16121194)
• The effect of PDE4 on the of action of PKA on GRK2 phosphorylation and transport is reported. (PMID:16356165)
• The presence of the alpha(2C)AR within the heterodimer resulted in a marked reduction in the level of GRK2-mediated alpha(2A)AR phosphorylation, which was accompanied by a qualitative attenuation of beta-arrestin recruitment. (PMID:16605244)
• Our results suggest a feedback mechanism by which phosphorylation of GRK2 by c-Src increases both GRK2 kinase activity towards GPCRs and its specific interaction with Galphaq subunits. (PMID:16725308)
• High expression was detected in septic neutrophils and control cells treated with cytokines plus LPS. (PMID:16849637)
• clathrin has a role in phosphorylation and internalization of beta2-adrenergic receptor by GRK2 (PMID:16920721)
• Decreased expression of GRK2 is associated with obstructed bladder (PMID:16984558)
• Overexpression of GRK2 in Alzheimer disease. (PMID:17000469)
• insulin-like growth factor-1 alters Mdm2-mediated GRK2 degradation, leading to enhanced GRK2 stability and increased kinase levels (PMID:17006543)
• analysis of the G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor (PMID:17008309)
• Phosphorylation of p38 by GRK2 at the docking groove unveils a novel mechanism for inactivating p38MAPK. (PMID:17055984)
• interaction of DREAM with GRK6 and GRK2, members of the G protein-coupled receptor kinase family of proteins, and their phosphorylation of DREAM (PMID:17102134)
• Our studies indicate that GRK2 is a novel component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding. GRK2 may play a role in hyperphosphorylation of tau in tauopathies. (PMID:17146290)
• Our data suggest that in cirrhosis-induced vasodilation, the AT1-R is desensitized by GRK-2 and beta-arrestin-2 and that changed patterns of phosphorylated Ca(2+) sensitizing proteins decrease Ca(2+) sensitivity. (PMID:17256744)
• Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. (PMID:17276003)
• findings show in tissues that S-nitrosothiols (SNOs) increase beta-adrenergic receptor (beta-AR) expression and prevent agonist-stimulated receptor (PMID:17482545)
• GRK2 interacts not only with epithelial Na(+) channels, but also with both Nedd4 and Nedd4-2. (PMID:17544362)
• Mechanical unloading leads to complete reversal in PI3Kgamma and betaARK1-associated PI3K activation. Furthermore, displacement of active PI3K from betaARK1 restores betaAR responsiveness in failing myocytes. (PMID:17998459)
• Regulator of coordinated integrin and G-protein-coupled receptor-directed epithelial cell migration. (PMID:18369319)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Grk2	ENSMUSG00000024858
rattus_norvegicus	Grk2	ENSRNOG00000018985
drosophila_melanogaster	Gprk1	FBGN0260798
drosophila_melanogaster	Gprk2	FBGN0261988
caenorhabditis_elegans		WBGENE00001708
caenorhabditis_elegans		WBGENE00001709

Paralogs (7): GRK3 (ENSG00000100077), GRK7 (ENSG00000114124), GRK4 (ENSG00000125388), RSKR (ENSG00000167524), GRK1 (ENSG00000185974), GRK6 (ENSG00000198055), GRK5 (ENSG00000198873)

Protein

Protein identifiers

Beta-adrenergic receptor kinase 1 — P25098 (reviewed: P25098)

Alternative names: G-protein coupled receptor kinase 2

All UniProt accessions (4): P25098, A0A0S2Z392, A0A0S2Z3I6, E9PRV7

UniProt curated annotations — full annotation on UniProt →

Function. Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Phosphorylates catecholamine-activated ADRB2 to regulate physiological cardiomyocyte contraction rate responses. Also phosphorylates ligand-bound C3a and C5a anaphylatoxin receptors (C3AR1 and C5AR1, respectively), leading to receptor desensitization. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner. Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity. Inhibits relaxation of airway smooth muscle in response to blue light.

Subunit / interactions. Interacts with the heterodimer formed by GNB1 and GNG2. Interacts with GIT1. Interacts with, and phosphorylates chemokine-stimulated CCR5. Interacts with ARRB1. Interacts with LPAR1 and LPAR2. Interacts with RALA in response to LPAR1 activation. ADRBK1 and RALA mutually inhibit each other’s binding to LPAR1. Interacts with ADRB2.

Subcellular location. Cytoplasm. Cell membrane. Postsynapse. Presynapse.

Tissue specificity. Expressed in peripheral blood leukocytes.

Activity regulation. In contrast to other AGC family kinases, the catalytic activity is solely regulated by the binding of substrates and ligands, not by phosphorylation of the kinase domain.

Domain organisation. The PH domain binds anionic phospholipids and helps recruiting ADRBK1 from the cytoplasm to plasma membrane close to activated receptors. It mediates binding to G protein beta and gamma subunits, competing with G-alpha subunits and other G-betagamma effectors.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.

RefSeq proteins (1): NP_001610* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000239	GPCR_kinase	Family
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR001849	PH_domain	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016137	RGS	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00069, PF00169, PF00615

Enzyme classification (BRENDA):

• EC 2.7.11.15 — beta-adrenergic-receptor kinase (BRENDA: 10 organisms, 296 substrates, 190 inhibitors, 32 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.017–0.149	6
RHODOPSIN	0.0038–0.014	4
DEMEFTEAESNMN	0.0339	3
DEMEFTEAESNMNDLVSEYQ	0.0324	2
GEGMDEMEFTEAESNMN	0.1	2
RRREEEEESAAA	0.72–1.34	2
BETA-ADRENERGIC RECEPTOR	0.0003	1
EEMEFSEAEANMN	0.054	1
RRRAEASAA	5.1	1
RRRASAAASAA	3.3	1
RRRASASAA	5.4	1
RRRASPAAASAA	4.6	1
RRRASPASAA	3.4	1

Catalyzed reactions (Rhea), 1 shown:

• [beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-phosphate + ADP + H(+) (RHEA:19429)

UniProt features (96 total): helix 33, strand 26, turn 10, mutagenesis site 8, domain 4, sequence conflict 4, site 3, sequence variant 2, binding site 2, chain 1, modified residue 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
3V5W	X-RAY DIFFRACTION	2.07
5UKL	X-RAY DIFFRACTION	2.15
5WG4	X-RAY DIFFRACTION	2.31
4MK0	X-RAY DIFFRACTION	2.4
6U7C	X-RAY DIFFRACTION	2.44
7K7L	X-RAY DIFFRACTION	2.54
4PNK	X-RAY DIFFRACTION	2.56
5UKK	X-RAY DIFFRACTION	2.6
7PWD	X-RAY DIFFRACTION	2.6
7K7Z	X-RAY DIFFRACTION	2.61
5UVC	X-RAY DIFFRACTION	2.65
5UUU	X-RAY DIFFRACTION	2.7
6C2Y	X-RAY DIFFRACTION	2.74
3CIK	X-RAY DIFFRACTION	2.75
5WG3	X-RAY DIFFRACTION	2.9
3KRW	X-RAY DIFFRACTION	2.9
3KRX	X-RAY DIFFRACTION	3.1
5WG5	X-RAY DIFFRACTION	3.1
5HE1	X-RAY DIFFRACTION	3.15
1BAK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25098-F1	90.36	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 4 (required for receptor phosphorylation); 10 (required for receptor phosphorylation); 317 (proton acceptor); 3 (required for receptor phosphorylation)

Ligand- & substrate-binding residues (2): 197–205; 220

Post-translational modifications (1): 670

Mutagenesis-validated functional residues (8):

Position	Phenotype
3	85% reduction in phosphorylation of g-protein coupled receptor rhodopsin.
3	95% reduction in phosphorylation of g-protein coupled receptor rhodopsin. 60% reduction in phosphorylation of beta-2 adr
3	60% reduction in phosphorylation of g-protein coupled receptor rhodopsin.
4	95% reduction in phosphorylation of g-protein coupled receptor rhodopsin. 90% reduction in phosphorylation of beta-2 adr
4	95% reduction in phosphorylation of g-protein coupled receptor rhodopsin.
5	50% reduction in phosphorylation of g-protein coupled receptor rhodopsin.
7–8	95% reduction in phosphorylation of g-protein coupled receptor rhodopsin.
10	95% reduction in phosphorylation of g-protein coupled receptor rhodopsin and beta-2 adrenergic receptor adrb2. does not

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-111933	Calmodulin induced events
R-HSA-416476	G alpha (q) signalling events
R-HSA-418555	G alpha (s) signalling events
R-HSA-5635838	Activation of SMO
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-111885	Opioid Signalling
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-199991	Membrane Trafficking
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-418594	G alpha (i) signalling events
R-HSA-5358351	Signaling by Hedgehog
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-5653656	Vesicle-mediated transport
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 275 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, BIOCARTA_BARRESTIN_SRC_PATHWAY, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, AP4_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr11q13, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION

GO Biological Process (16): regulation of the force of heart contraction (GO:0002026), desensitization of G protein-coupled receptor signaling pathway (GO:0002029), negative regulation of the force of heart contraction by chemical signal (GO:0003108), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), tachykinin receptor signaling pathway (GO:0007217), heart development (GO:0007507), viral genome replication (GO:0019079), receptor internalization (GO:0031623), positive regulation of catecholamine secretion (GO:0033605), negative regulation of striated muscle contraction (GO:0045988), symbiont entry into host cell (GO:0046718), cardiac muscle contraction (GO:0060048), negative regulation of relaxation of smooth muscle (GO:1901081), protein phosphorylation (GO:0006468), signal transduction (GO:0007165)

GO Molecular Function (12): G protein-coupled receptor binding (GO:0001664), protein kinase activity (GO:0004672), G protein-coupled receptor kinase activity (GO:0004703), ATP binding (GO:0005524), alpha-2A adrenergic receptor binding (GO:0031694), Edg-2 lysophosphatidic acid receptor binding (GO:0031755), beta-adrenergic receptor kinase activity (GO:0047696), nucleotide binding (GO:0000166), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), cytoplasmic side of mitochondrial outer membrane (GO:0032473), presynapse (GO:0098793), postsynapse (GO:0098794), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
GPCR downstream signalling	3
Signal Transduction	2
CaM pathway	1
Hedgehog ‘on’ state	1
Clathrin-mediated endocytosis	1
G alpha (i) signalling events	1
PLC beta mediated events	1
Ca-dependent events	1
DAG and IP3 signaling	1
Opioid Signalling	1
G-protein mediated events	1
Intracellular signaling by second messengers	1
Vesicle-mediated transport	1
Signaling by GPCR	1
Signaling by Hedgehog	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
G protein-coupled receptor signaling pathway	2
viral life cycle	2
striated muscle contraction	2
protein kinase activity	2
synapse	2
regulation of heart contraction	1
regulation of biological quality	1
negative adaptation of signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
regulation of the force of heart contraction by chemical signal	1
negative regulation of heart contraction	1
G protein-coupled receptor activity	1
signal transduction	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
animal organ development	1
circulatory system development	1
viral process	1
receptor-mediated endocytosis	1
catecholamine secretion	1
regulation of catecholamine secretion	1
positive regulation of amine transport	1
positive regulation of secretion by cell	1
regulation of striated muscle contraction	1
negative regulation of muscle contraction	1
symbiont entry into host	1
heart contraction	1
relaxation of smooth muscle	1
negative regulation of relaxation of muscle	1
regulation of relaxation of smooth muscle	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor binding	1
kinase activity	1

Protein interactions and networks

STRING

2380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRK2	GNAQ	P50148	995
GRK2	GIT1	Q9Y2X7	993
GRK2	ARRB2	P32121	991
GRK2	ARRB1	P49407	982
GRK2	SUCLG2	Q96I99	939
GRK2	PEBP1	P30086	923
GRK2	ADRB2	P07550	913
GRK2	SAG	P10523	909
GRK2	CXCR2	P25025	872
GRK2	SMO	Q99835	844
GRK2	ARR3	P36575	836
GRK2	MAP2K1	Q02750	825
GRK2	RHO	P08100	819
GRK2	RGS11	O94810	776
GRK2	RGS6	P49758	772

IntAct

71 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GRK2	GRK3	psi-mi:“MI:0915”(physical association)	0.690
NFKBIA	GRK2	psi-mi:“MI:0407”(direct interaction)	0.560
GRK2	CSNK1D	psi-mi:“MI:0915”(physical association)	0.560
GRK2	ERBB3	psi-mi:“MI:0915”(physical association)	0.560
GRK2	NCAM1	psi-mi:“MI:0915”(physical association)	0.560
APP	GRK2	psi-mi:“MI:0915”(physical association)	0.560
PPP1R16B	ZNF24	psi-mi:“MI:0914”(association)	0.530
GRK2	UBC	psi-mi:“MI:0915”(physical association)	0.520
UBC	GRK2	psi-mi:“MI:0915”(physical association)	0.520
PTCH1	GRK2	psi-mi:“MI:0915”(physical association)	0.500
PTCH1	CCNB1	psi-mi:“MI:0914”(association)	0.500
GRK2	FPR1	psi-mi:“MI:0915”(physical association)	0.500
FPR1	MAPK13	psi-mi:“MI:0914”(association)	0.500
GRK2	EGFR	psi-mi:“MI:0915”(physical association)	0.460
EGFR	GRK2	psi-mi:“MI:0915”(physical association)	0.460

BioGRID (162): ADRBK1 (Affinity Capture-RNA), ADRBK1 (Co-fractionation), ADRBK1 (Co-fractionation), ADRBK1 (Co-fractionation), ADRBK1 (Co-fractionation), ADRBK1 (Co-fractionation), ADRBK1 (Co-fractionation), ADRBK1 (Co-fractionation), NARS2 (Co-fractionation), ADRBK1 (Affinity Capture-MS), ADRBK1 (Affinity Capture-MS), ADRBK1 (Affinity Capture-MS), ADRBK1 (Affinity Capture-MS), ADRBK1 (Affinity Capture-MS), ADRBK1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9X0, A8WUG4, F1M7Y5, O08875, O13310, O15075, O19111, O97627, P00518, P07934, P09217, P21146, P25098, P26817, P26818, P26819, P31325, P34722, P35626, P41743, P54645, P54646, P83099, Q02111, Q02956, Q04735, Q05513, Q09137, Q09639, Q11179, Q12706, Q13131, Q16816, Q19266, Q21734, Q28948, Q39019, Q3UYH7, Q5EG47, Q5R4K9

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A8X775, B1WAR9, C4YRB7, D2HXI8, E1C2I2, E9PSL7, G1X456, G5EGQ3, M3TYT0, O00506, O01583, O01700, O14578, O54874, O61267, O75116, O77819, O80902, O88643, O97627, P05131, P0CY23, P0CY24, P13677, P21146, P25098, P26817, P26818, P32865, P34100, P35465, P38070, P48562, P49025, P49673, P54265, P70335

SIGNOR signaling

73 interactions.

A	Effect	B	Mechanism
GRK2	up-regulates	SMO	phosphorylation
GRK2	up-regulates	EZR	phosphorylation
GRK2	down-regulates	MAPK14	phosphorylation
CDK2	down-regulates	GRK2	phosphorylation
GRK2	unknown	CLTB	phosphorylation
GRK2	“down-regulates activity”	MC4R	phosphorylation
GRK2	“down-regulates activity”	OPRM1	phosphorylation
GRK2	“up-regulates activity”	PDE6G	phosphorylation
PRKCA	“up-regulates activity”	GRK2	phosphorylation
PRKCD	“up-regulates activity”	GRK2	phosphorylation
PRKCG	“up-regulates activity”	GRK2	phosphorylation
GRK2	“down-regulates activity”	OPRD1	phosphorylation
GRK2	“down-regulates activity”	BDKRB2	phosphorylation
NCS1	“down-regulates activity”	GRK2	binding
SRC	“up-regulates activity”	GRK2	phosphorylation
GRK2	“down-regulates activity”	TBXA2R	phosphorylation
GRK2	“up-regulates activity”	STK3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ERBB2 TMD/JMD mutants	5	56.6×	7e-06
Downregulation of ERBB2 signaling	6	54.4×	6e-07
Signaling by ERBB2 KD Mutants	5	50.4×	9e-06
Signaling by ERBB2	5	41.2×	9e-06
Aggrephagy	5	29.6×	3e-05
Regulation of PLK1 Activity at G2/M Transition	6	18.1×	3e-05
RAF/MAP kinase cascade	6	8.7×	1e-03
PIP3 activates AKT signaling	5	8.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

49 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	6
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1184830	NM_001619.5(GRK2):c.469C>T (p.Leu157Phe)	Pathogenic
1184831	NM_001619.5(GRK2):c.1348_1349del (p.Ser450fs)	Likely pathogenic
1184832	NM_001619.5(GRK2):c.555+1G>A	Likely pathogenic

SpliceAI

3048 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67266810:CAGGT:C	donor_loss	1.0000
11:67266812:GGTGA:G	donor_loss	1.0000
11:67266813:G:T	donor_loss	1.0000
11:67266814:T:G	donor_loss	1.0000
11:67272542:G:GT	donor_gain	1.0000
11:67277344:GCTGG:G	donor_gain	1.0000
11:67277349:G:GG	donor_gain	1.0000
11:67279198:AG:A	acceptor_gain	1.0000
11:67279199:GG:G	acceptor_gain	1.0000
11:67279271:G:GT	donor_gain	1.0000
11:67279413:TCCAG:T	acceptor_loss	1.0000
11:67279416:A:AG	acceptor_gain	1.0000
11:67279417:G:GC	acceptor_gain	1.0000
11:67279515:CGCAT:C	donor_gain	1.0000
11:67279516:GCAT:G	donor_gain	1.0000
11:67279516:GCATG:G	donor_gain	1.0000
11:67279517:CAT:C	donor_gain	1.0000
11:67279518:AT:A	donor_gain	1.0000
11:67279519:TG:T	donor_loss	1.0000
11:67279520:G:GA	donor_loss	1.0000
11:67279520:G:GG	donor_gain	1.0000
11:67279521:TGAG:T	donor_loss	1.0000
11:67279522:GAGT:G	donor_loss	1.0000
11:67279621:CCCA:C	acceptor_loss	1.0000
11:67279622:CCA:C	acceptor_loss	1.0000
11:67279623:CA:C	acceptor_loss	1.0000
11:67279624:A:AG	acceptor_gain	1.0000
11:67279624:A:T	acceptor_loss	1.0000
11:67279625:G:GA	acceptor_gain	1.0000
11:67279625:GC:G	acceptor_gain	1.0000

AlphaMissense

4579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67266722:T:A	L8Q	1.000
11:67266722:T:C	L8P	1.000
11:67266724:G:C	A9P	1.000
11:67266727:G:C	D10H	1.000
11:67266727:G:T	D10Y	1.000
11:67266728:A:C	D10A	1.000
11:67266728:A:T	D10V	1.000
11:67266736:T:C	Y13H	1.000
11:67266740:T:C	L14P	1.000
11:67280757:T:A	W177R	1.000
11:67280757:T:C	W177R	1.000
11:67281108:T:C	F191L	1.000
11:67281109:T:C	F191S	1.000
11:67281110:C:A	F191L	1.000
11:67281110:C:G	F191L	1.000
11:67281117:C:G	H194D	1.000
11:67281120:C:A	R195S	1.000
11:67281121:G:C	R195P	1.000
11:67281121:G:T	R195L	1.000
11:67281124:T:G	I196S	1.000
11:67281127:T:A	I197N	1.000
11:67281129:G:A	G198R	1.000
11:67281129:G:C	G198R	1.000
11:67281129:G:T	G198W	1.000
11:67281130:G:A	G198E	1.000
11:67281130:G:C	G198A	1.000
11:67281130:G:T	G198V	1.000
11:67281132:C:A	R199S	1.000
11:67281133:G:C	R199P	1.000
11:67281135:G:A	G200R	1.000

dbSNP variants (sampled 300 via entrez): RS1000454302 (11:67277568 C>T), RS1000570063 (11:67278372 G>A), RS1000623837 (11:67278726 T>C), RS1000807718 (11:67284523 G>A,T), RS1000838642 (11:67268757 A>G,T), RS1001155134 (11:67284059 T>C), RS1001200029 (11:67282097 C>G,T), RS1001339275 (11:67270025 C>A,G,T), RS1001420435 (11:67273417 A>T), RS1001541061 (11:67284646 G>A), RS1001766283 (11:67272686 CT>C), RS1001790195 (11:67270323 C>T), RS1001818530 (11:67272949 G>A), RS1001898640 (11:67273875 C>T), RS1001951106 (11:67274187 A>G)

Disease associations

OMIM: gene MIM:109635 | disease phenotypes: MIM:208500

GenCC curated gene-disease

Disease	Classification	Inheritance
Jeune syndrome	Moderate	Autosomal recessive

Mondo (2): Jeune syndrome (MONDO:0018770), Jeune syndrome - GRK2-related (MONDO:0100583)

Orphanet (1): Jeune syndrome (Orphanet:474)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004630_176	Mean corpuscular hemoglobin	2.000000e-14
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004341	body fat distribution

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537571	Jeune syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4079 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 51,261 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL490	PAROXETINE	4	46,410
CHEMBL6067650	PAROXETINE HYDROCHLORIDE	4	439
CHEMBL3544964	RAVOXERTINIB	2	1,243
CHEMBL3128043	PF-03758309	1	233
CHEMBL3544960	AT-13148	1	779

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Beta-adrenergic receptor kinases (βARKs)

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
CCG258747	Inhibition	7.74	pIC50
balanol	Inhibition	7.38	pIC50
compound 101 [PMID: 21596927]	Inhibition	7.27	pIC50
compound 1o [PMID: 24210504]	Inhibition	6.34	pIC50
GSK180736A	Inhibition	6.11	pIC50

Binding affinities (BindingDB)

80 measured of 88 human assays (95 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1R)-1-[3-fluoro-4-[(1-hydroxy-7-methyl-3H-2,1-benzoxaborol-6-yl)oxy]phenyl]ethanamine	IC50	13.9 nM	US-9493490: Boron-containing small molecules
4-[4-fluoro-3-[(2-methoxyphenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	60 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
SMR000230206	EC50	60 nM
4-[3-[(2,6-dimethylphenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	70 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-difluorophenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	120 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-dichlorophenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	130 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-dimethoxyphenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	130 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(pyridin-2-ylmethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	150 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E22	IC50	180 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(3-fluorophenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[2-(2,6-dimethylphenyl)ethylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	230 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E24	IC50	240 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(2-pyridin-2-ylethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	280 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E27	IC50	320 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(3-methoxyphenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	420 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[2-[(2,6-dimethoxyphenyl)methylamino]-2-oxoethyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	450 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(4-methoxyphenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	460 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E32	IC50	500 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E33	IC50	680 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-(benzylcarbamoyl)-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	690 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
MLS001030305	EC50	700 nM
N-[6-azanyl-2,4-bis(oxidanylidene)-1-(phenylmethyl)pyrimidin-5-yl]-N-propyl-3-pyrrol-1-yl-benzamide	EC50	720 nM
E20	IC50	740 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
GSK-180736A	IC50	770 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E23	IC50	820 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E35	IC50	960 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
2-[3-[2-hydroxyethyl(dimethyl)azaniumyl]propanoylamino]-2-methyl-propane-1-sulfonate	EC50	1160 nM
E26	IC50	1200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E34	IC50	1200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[[2,6-bis(trifluoromethyl)phenyl]methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	1200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
2-[5-[(Z)-(3-bromanyl-8-oxidanylidene-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-7-ylidene)methyl]furan-2-yl]benzoic acid	IC50	1250 nM
E31	IC50	1500 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
(8S)-7-(4-chlorobenzoyl)-3-(3-methacrylamidophenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	1540 nM
4-[4-fluoro-3-[(3-methyl-2-pyridinyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	1900 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
(8S)-7-(3,3-diphenylpropanoyl)-3-[3-(2-methylprop-2-enoylamino)phenyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	EC50	1940 nM
1-Chloro-2-(2-nitro-phenylsulfanyl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[c]quinoline-4,6-dicarboxylic acid	IC50	2170 nM
E36	IC50	2600 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(isoquinolin-1-ylmethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	2600 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[[3,5-bis(trifluoromethyl)phenyl]methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	2700 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
2-chloranyl-4-[5-[(1-oxidanylidene-[1,3]thiazolo[3,2-a]benzimidazol-2-ylidene)methyl]furan-2-yl]benzoic acid	IC50	2890 nM
MLS000561998	EC50	2960 nM
SMR000542887	EC50	3050 nM
(8R)-3-[3-[(2-methyl-1-oxoprop-2-enyl)amino]phenyl]-7-(1-oxo-2,2-diphenylethyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	3120 nM
(8R)-3-[3-[(2-methyl-1-oxoprop-2-enyl)amino]phenyl]-7-[(E)-1-oxobut-2-enyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	IC50	3480 nM
SMR000621519	EC50	3620 nM
2-[(3-bromoanilino)-oxomethyl]-1-cyclohexanecarboxylic acid	EC50	3850 nM
E37	IC50	4000 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
2-(tert-butylamino)-1-phenylethan-1-ol, 4	KD	4100 nM
4-[4-fluoro-3-(methylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	4300 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
(8S)-7-[(4-methoxyphenyl)-oxomethyl]-3-[3-(1-oxohexylamino)phenyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	EC50	4380 nM

ChEMBL bioactivities

437 potent at pChembl≥5 of 501 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.92	IC50	1.2	nM	CHEMBL1738878
8.77	IC50	1.7	nM	CHEMBL4073882
8.74	IC50	1.8	nM	CHEMBL4072828
8.72	IC50	1.9	nM	CHEMBL4086046
8.70	IC50	2	nM	CHEMBL3716385
8.70	Kd	1.99	nM	CHEMBL1738878
8.55	IC50	2.8	nM	CHEMBL3718650
8.52	IC50	3	nM	CHEMBL4095659
8.49	IC50	3.2	nM	CHEMBL3716440
8.49	IC50	3.2	nM	CHEMBL3719041
8.43	IC50	3.7	nM	CHEMBL3718067
8.41	IC50	3.9	nM	CHEMBL3718984
8.41	IC50	3.9	nM	CHEMBL3718849
8.41	IC50	3.9	nM	CHEMBL4077447
8.40	IC50	4	nM	CHEMBL3716298
8.35	IC50	4.5	nM	CHEMBL3719096
8.34	IC50	4.6	nM	CHEMBL3715310
8.26	IC50	5.5	nM	CHEMBL4071398
8.22	IC50	6	nM	CHEMBL4742990
8.21	IC50	6.2	nM	CHEMBL3714916
8.21	IC50	6.1	nM	CHEMBL4082775
8.20	IC50	6.3	nM	CHEMBL3717041
8.19	IC50	6.4	nM	CHEMBL3716102
8.17	IC50	6.8	nM	CHEMBL4103972
8.12	IC50	7.5	nM	CHEMBL3717989
8.12	IC50	7.5	nM	CHEMBL4083276
8.11	IC50	7.8	nM	CHEMBL3718495
8.11	IC50	7.7	nM	CHEMBL3716137
8.11	IC50	7.7	nM	CHEMBL3716175
8.11	IC50	7.7	nM	CHEMBL3717935
8.11	IC50	7.8	nM	CHEMBL4094447
8.10	IC50	8	nM	CHEMBL3719183
8.10	IC50	7.9	nM	CHEMBL3716523
8.08	IC50	8.3	nM	CHEMBL3716346
8.08	IC50	8.3	nM	CHEMBL3716850
8.06	IC50	8.8	nM	CHEMBL3716615
8.06	IC50	8.8	nM	CHEMBL3716279
8.06	IC50	8.7	nM	CHEMBL3719241
8.06	IC50	8.7	nM	CHEMBL3715386
8.05	IC50	9	nM	CHEMBL4785990
8.03	IC50	9.3	nM	CHEMBL3715431
8.03	IC50	9.3	nM	CHEMBL3717691
8.01	IC50	9.8	nM	CHEMBL3714810
8.00	IC50	9.9	nM	CHEMBL3716786
8.00	Ki	10	nM	CHEMBL3731835
8.00	Ki	10	nM	CHEMBL3732726
8.00	Ki	10	nM	CHEMBL3728531
8.00	Ki	10	nM	CHEMBL3728772
8.00	Ki	10	nM	CHEMBL3729453
8.00	Ki	10	nM	CHEMBL3732468

PubChem BioAssay actives

249 with measured affinity, of 743 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(2,6-difluorophenyl)methyl]-3-[(4-propyl-5-pyrimidin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0012	uM
N-[(2,6-difluorophenyl)methyl]-3-(9-oxa-3,4,6,12-tetrazatricyclo[8.4.0.02,6]tetradeca-1(10),2,4,11,13-pentaen-5-ylmethylamino)benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0017	uM
3-(9-oxa-3,4,6,12-tetrazatricyclo[8.4.0.02,6]tetradeca-1(10),2,4,11,13-pentaen-5-ylmethylamino)-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0018	uM
3-[(4-propyl-5-pyrimidin-4-yl-1,2,4-triazol-3-yl)methylamino]-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0019	uM
N-[(2-methoxyphenyl)methyl]-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0030	uM
N-[(2-chlorophenyl)methyl]-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0039	uM
3-[[4-(2-hydroxyethyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]methylamino]-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0055	uM
3-[(3-methoxyphenyl)methyl]-6-(1H-pyrazol-4-yl)quinazolin-4-one	1698821: Inhibition of human GRK2 by LANCE assay	ic50	0.0060	uM
N-benzyl-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0061	uM
N-[(2,6-difluorophenyl)methyl]-3-[(4-methyl-5-pyrimidin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0068	uM
N-benzyl-3-[(4-ethyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0075	uM
3-[(4-methyl-5-pyrimidin-4-yl-1,2,4-triazol-3-yl)methylamino]-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0078	uM
N-(4-fluorophenyl)-3-[[4-oxo-6-(1H-pyrazol-4-yl)quinazolin-3-yl]methyl]benzamide	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0090	uM
N-benzyl-3-[(4-methyl-3-pyridin-4-yl-1H-pyrazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0099	uM
N-[(4-fluorophenyl)methyl]-3-[[4-oxo-6-(1H-pyrazol-4-yl)quinazolin-3-yl]methyl]benzamide	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0100	uM
N-[(2,6-difluorophenyl)methyl]-3-[[4-oxo-6-(1H-pyrazol-4-yl)quinazolin-3-yl]methyl]benzamide	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0100	uM
5-[5-(hydroxymethyl)-3-pyridinyl]-N-(oxan-4-ylmethyl)-1H-indazole-3-carboxamide	1655581: Inhibition of human GRK2 in presence of ATP	ic50	0.0110	uM
N-[(3-methoxyphenyl)methyl]-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0120	uM
N-[(2-chlorophenyl)methyl]-3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0120	uM
N-[2-chloro-5-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]phenyl]-2-phenylacetamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0120	uM
3-[1-(3-methoxyphenyl)-3-(methylamino)propyl]-6-(1H-pyrazol-4-yl)quinazolin-4-one	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0120	uM
3-[(1R)-1-(3-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)quinazolin-4-one	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0130	uM
N-benzyl-3-[(3-pyridin-4-yl-1H-pyrazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0140	uM
N-[(E)-7,8-dihydro-6H-isoquinolin-5-ylideneamino]-2-(3-methoxyanilino)acetamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0140	uM
N-benzyl-3-[[4-(2-methoxyethyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0160	uM
N-[(4-methoxyphenyl)methyl]-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0170	uM
3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0180	uM
5-[(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)piperidin-4-yl]-2-fluoro-N-(2H-indazol-3-ylmethyl)benzamide	2000127: Inhibition of human GRK2	ic50	0.0180	uM
3-[(4-fluoro-3-methoxyphenyl)methyl]-6-(1H-pyrazol-4-yl)quinazolin-4-one	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0180	uM
1-benzyl-3-[3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]phenyl]urea	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0190	uM
2-[(3-methoxyphenyl)methyl]-7-(1H-pyrazol-4-yl)phthalazin-1-one	1698792: Inhibition of human GRK2 by transcreener assay	ic50	0.0190	uM
4-[3-[(2,6-dimethoxyphenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	2000130: Inhibition of GRK2 (unknown origin)	ic50	0.0200	uM
N-benzyl-3-[[2-[(2E)-2-(7,8-dihydro-6H-isoquinolin-5-ylidene)hydrazinyl]-2-oxoethyl]amino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0200	uM
N-benzyl-3-[(5-pyridin-4-yl-1H-imidazol-2-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0210	uM
N-(3-phenylpropyl)-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0230	uM
N-benzyl-3-[(5-pyridin-4-yl-1,2-oxazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0240	uM
5-[(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)piperidin-4-yl]-2-fluoro-N-(1H-pyrazol-5-ylmethyl)benzamide	2000127: Inhibition of human GRK2	ic50	0.0300	uM
N-benzyl-3-[(4-propyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0320	uM
N-(2-phenylethyl)-3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0380	uM
3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-N-[[3-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0390	uM
4-chloro-N-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methyl]aniline	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0410	uM
N-benzyl-3-[[3-(3-methyl-4-pyridinyl)-1H-1,2,4-triazol-5-yl]methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0420	uM
N-[(E)-7,8-dihydro-6H-isoquinolin-5-ylideneamino]-2-(3-phenoxyanilino)acetamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0420	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	2000130: Inhibition of GRK2 (unknown origin)	ic50	0.0420	uM
3-[(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)methylamino]benzenesulfonamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0440	uM
N-[(2-methoxyphenyl)methyl]-3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0440	uM
3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-N-[[4-(trifluoromethyl)phenyl]methyl]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0450	uM
N-benzyl-3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0450	uM
N-benzyl-3-[(3-pyridin-4-yl-1,2-oxazol-5-yl)methylamino]benzamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0460	uM
2-(3-methoxyanilino)-N-[(E)-pyridin-4-ylmethylideneamino]acetamide	1457939: Inhibition of recombinant human N-terminal GST-tagged GRK2 expressed in baculovirus expression system using ulight topo2alpha as substrate preincubated for 60 mins followed by substrate addition measured after 10 mins by Lance TR-FRET assay	ic50	0.0490	uM

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Propranolol	decreases expression, affects cotreatment, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
ICI 118551	increases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol	affects localization, affects reaction, increases reaction, affects cotreatment	1
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone	affects localization, affects reaction, increases reaction	1
glyceryl 2-arachidonate	affects cotreatment, affects localization, affects reaction, increases reaction	1
2-palmitoylglycerol	increases expression	1
(N)-methanocarba-2MeSADP	decreases reaction, increases activity, increases phosphorylation	1
gardiquimod	increases expression, decreases reaction	1
Carvedilol	affects cotreatment, increases expression	1
Cyclic AMP	increases chemical synthesis, increases reaction, affects binding, increases activity	1
Air Pollutants	increases abundance, affects expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Diuron	decreases expression	1
Dopamine	affects localization, increases reaction	1
Doxorubicin	decreases expression	1
Epinephrine	increases phosphorylation, increases reaction	1
Isoproterenol	increases expression	1
Ozone	affects expression, increases abundance	1
Pesticides	decreases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

206 unique, capped per target: 206 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037594	Binding	Residual activity of GRK2 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2Y8	Abcam HEK293T GRK2 KO	Transformed cell line	Female
CVCL_D7R0	Ubigene A-549 GRK2 KO	Cancer cell line	Male
CVCL_D8M5	Ubigene HCT 116 GRK2 KO	Cancer cell line	Male
CVCL_D9FV	Ubigene HEK293 GRK2 KO	Transformed cell line	Female
CVCL_E0E3	Ubigene HeLa GRK2 KO	Cancer cell line	Female
CVCL_SB81	HAP1 ADRBK1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

3 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)