ADRB2

Summary

ADRB2 (adrenoceptor beta 2, HGNC:286) is a protein-coding gene on chromosome 5q32, encoding Beta-2 adrenergic receptor (P07550). G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways.

This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson’s Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease.

Source: NCBI Gene 154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited susceptibility to asthma (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 42 total
• Druggable target: yes — 166 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:286
Approved symbol	ADRB2
Name	adrenoceptor beta 2
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	ADRBR, BAR, B2AR, ARB2
Ensembl gene	ENSG00000169252
Ensembl biotype	protein_coding
OMIM	109690
Entrez	154

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000305988

RefSeq mRNA: 1 — MANE Select: NM_000024 NM_000024

CCDS: CCDS4292

Canonical transcript exons

ENST00000305988 — 1 exons

Exon	Start	End
ENSE00001154479	148826611	148828623

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 94.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9587 / max 1688.7395, expressed in 1252 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59320	17.5788	1250
59322	0.1440	18
59323	0.1372	32
59321	0.0987	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	94.21	gold quality
granulocyte	CL:0000094	94.18	gold quality
upper leg skin	UBERON:0004262	93.09	gold quality
gingival epithelium	UBERON:0001949	91.02	gold quality
cervix squamous epithelium	UBERON:0006922	90.31	gold quality
gingiva	UBERON:0001828	90.09	gold quality
squamous epithelium	UBERON:0006914	90.01	gold quality
palpebral conjunctiva	UBERON:0001812	89.84	gold quality
esophagus squamous epithelium	UBERON:0006920	89.01	gold quality
skin of abdomen	UBERON:0001416	88.82	gold quality
lower lobe of lung	UBERON:0008949	88.80	gold quality
epithelium of esophagus	UBERON:0001976	87.35	gold quality
skin of leg	UBERON:0001511	87.23	gold quality
omental fat pad	UBERON:0010414	86.80	gold quality
peritoneum	UBERON:0002358	86.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.61	gold quality
right lung	UBERON:0002167	86.57	gold quality
zone of skin	UBERON:0000014	86.25	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.86	gold quality
cervix epithelium	UBERON:0004801	85.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.39	gold quality
biceps brachii	UBERON:0001507	85.33	gold quality
adipose tissue	UBERON:0001013	85.17	gold quality
upper lobe of left lung	UBERON:0008952	85.11	gold quality
upper lobe of lung	UBERON:0008948	85.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.86	gold quality
connective tissue	UBERON:0002384	84.79	gold quality
leukocyte	CL:0000738	83.82	gold quality
lung	UBERON:0002048	83.39	gold quality
blood	UBERON:0000178	83.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BCL3, CEBPA, EZH2, FOXC1, HIC1

miRNA regulators (miRDB)

92 targeting ADRB2, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 40)

• the allelic frequency of beta2-adrenergic receptor gene mutation in codons 16 and 27 did not differ between obese subjects and non-obese (PMID:11718682)
• The distribution of the SNP genotype AA, GA and GG at position 1023 in the severe hypertension group was significantly different from that in normal group. (PMID:11798846)
• sequestration caused by Akt and insulin (PMID:11809767)
• The beta2-adrenoceptor (ADRB2) plays a pivotal role in signalling in relation to hypertension and obesity. Polymorphisms of the ADRB2 gene have been shown to be potentially related to essential hypertension and other non-cardiovascular disease phenotypes. (PMID:11821707)
• Regulation of beta2-adrenergic receptors on CD4 and CD8 positive lymphocytes by cytokines in vitro (PMID:11884023)
• 27Glu polymorphism of the beta2-adrenergic receptor gene interacts with physical activity influencing obesity risk among female subjects (PMID:12030897)
• the beta2-adrenergic receptor is associated with the propensity to gain weight from childhood to young adulthood in males (PMID:12080445)
• variation in asthma (review article) (PMID:12083965)
• beta1-adrenoceptor and beta2-adrenoceptor couple to Gs-proteins to activate adenylyl cyclase (PMID:12106601)
• role of heterodimerization with beta 1-adrenergic receptor regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy (PMID:12140284)
• polymorphic in cystic fibrosis (PMID:12142723)
• polymorphic in cystic fibrosis (PMID:12142724)
• assessment of binding and activation properties of Cys mutants (PMID:12167654)
• linkage analysis of ADRB2 polymorphisms does not support the role of this gene as a major causative gene for the detected linkage of human chromosome 5 with hypertension (PMID:12215468)
• Results indicate that the proportion of homo- and heterodimers between the closely related beta(1)- and beta(2)-adrenergic receptors is determined by their relative levels of expression. (PMID:12244098)
• beta(2)AR activation of ERK1/2 does not require PKA phosphorylation of the beta(2)AR, receptor internalization or switching from activation of G(s) to G(i) but clearly requires activation of a Src family member that may be downstream of PKA. (PMID:12391272)
• identified the Zn2+ binding site responsible for the positive effect of Zn2+ ions on agonist binding to the 2AR (PMID:12409304)
• Data report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. (PMID:12429837)
• data demonstrate that homozygosity for Arg16, which in vitro is associated with decreased down-regulation of the beta(2)AR, protects from preterm delivery (PMID:12439523)
• Effects of Arg16 Gly polymorphism on forearm blood flow responses to isoproterenol dependent on differences in endothelial generation of nitric oxide. Regional blood flow responses to isoproterenol greater in Gly16 than in Arg16 homozygotes. (PMID:12527744)
• No evidence of excess allele sharing identity by descent in sib pairs, revealing a lack of linkage between 2q14-q23 or 5q32 (chromosome region harboring the gene. encoding beta 2 adrenergic receptor) and hypertension in our study sample. (PMID:12569260)
• The Glu27 allele of the beta2-adrenergic receptor was associated with a lower risk of incident coronary events in an elderly population (PMID:12682000)
• Polymorphisms not significantly different in NIDDM compared with normal values. (PMID:12716862)
• lipolytic catecholamine resistance of sc adipocytes in polycystic ovary syndrome is probably due to a combination of decreased amounts of beta(2)-adrenergic receptors, the regulatory II beta-component of protein kinase A, and hormone-sensitive lipase (PMID:12727985)
• b2-AR 27Glu polymorphism has a protective effect against metabolic disorders in obese families from southern Poland. (PMID:12824951)
• lipolysis and fat oxidation promoted by a peak oxygen consumption test appear to be blunted in polymorphic Glu27Glu beta2 adrenergic receptor obese females (PMID:12832031)
• agonist-induced desensitization of cardiac beta2ARs is more pronounced in wild type than Thr164Ile polymorphism subjects. (PMID:12869379)
• Females with polymorphism and higher carbohydrate intake had higher obesity risk. High carbohydrate intake was associated with higher insulin levels among women with Gln27Glu polymorphism. (PMID:12888635)
• The association of genetic polymorphisms of ADRB2 with blood pressure-related and obesity-related phenotypes. (PMID:12900437)
• findings show that signaling via the erythrocyte beta2-adrenergic receptor and heterotrimeric guanine nucleotide-binding protein (Galphas) regulated the entry of the human malaria parasite Plasmodium falciparum (PMID:14500986)
• the Arg(16) and Gln(27) variants of the beta(2)-adrenergic receptor gene contribute to metabolic syndrome susceptibility in men. (PMID:14557466)
• down-regulation of beta(2)-AR protein with labor may constitute a contributory mechanism by which uterine quiescence is removed at term. (PMID:14557486)
• Beta2-adrenergic receptor variants are associated with spirometric values and bronchodilator responsiveness, but different regions of the gene provide evidence for association with these phenotypes. (PMID:14610472)
• variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma (PMID:14657864)
• Arg16/Gly polymorphism is associated with differences in acute pressor responses to sympathoexcitation (PMID:14665698)
• Increased sensitivity to catecholamine-induced lipolysis of Gly allele promotes higher free fatty acids concentrations in portal system, which could enhance higher levels of fasting insulin. (PMID:14693408)
• Insulin and beta-adrenergic agonists stimulate a rapid phosphorylation and sequestration of the beta2-adrenergic receptors (beta2ARs). (PMID:14709719)
• the beta2-AR genotype, both independently and interacting with habitual PA levels, is significantly associated with a-vDO2 during exercise in postmenopausal women (PMID:14715679)
• internalization of beta(1)AR is both arrestin- and dynamin-dependent and follows the same clathrin-mediated endocytic pathway as beta(2)AR (PMID:14734649)
• 3D structure of human beta2 adrenergic receptor predicts ligand-binding sites for epinephrine and norepinephrine. (PMID:14981238)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adrb2b	ENSDARG00000054510
danio_rerio	adrb2a	ENSDARG00000088124
mus_musculus	Adrb2	ENSMUSG00000045730
rattus_norvegicus	Adrb2	ENSRNOG00000019217
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), ADRA1A (ENSG00000120907), DRD2 (ENSG00000149295), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRA1B (ENSG00000170214), ADRA1D (ENSG00000171873), OR5T3 (ENSG00000172489), OR56A1 (ENSG00000180934), OR5T1 (ENSG00000181698), OR5T2 (ENSG00000181718), OR56A4 (ENSG00000183389), ADRA2C (ENSG00000184160), OR56A3 (ENSG00000184478), OR13F1 (ENSG00000186881), OR56A5 (ENSG00000188691), ADRB3 (ENSG00000188778), ADRA2B (ENSG00000274286)

Protein

Protein identifiers

Beta-2 adrenergic receptor — P07550 (reviewed: P07550)

Alternative names: Beta-2 adrenoreceptor

All UniProt accessions (2): P07550, X5DQM5

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways. ADRB2 binds epinephrine (Epi) with an approximately 30-fold greater affinity than norepinephrine (NE). In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte contraction rate, respectively. Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate. Epi also promotes ADRB2 coupling to G(i) proteins to exert cardioprotective effects especially in the conditions of hypoxia and oxidative stress through the G(i)/PI3K/Akt signaling pathway. ADRB2-G(s) signaling delivers proapoptotic signals in cardiomyocytes although G(i)-mediated survival effect appears to predominate. ADRB2 also transduces signals independently of PKA to regulate cellular pH by modulating Na(+)/H(+) exchanger SLC9A3 function.

Subunit / interactions. Binds NHERF1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC. Interacts with USP20 and USP33. Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. Interacts with CNIH4. Interacts with ARRDC3. Interacts with NEDD4. Interacts with MARCHF2.

Subcellular location. Cell membrane. Golgi apparatus.

Post-translational modifications. Palmitoylated. Mainly palmitoylated at Cys-341. Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation. Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi. Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor. Could be depalmitoylated by LYPLA1 at the plasma membrane. Phosphorylated by PKA and BARK/GRK2 upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK/GRK2. Distinct temporal phosphorylation on Ser-355 and Ser-356 by BARK/GRK2 plays a critical role for dictating receptor cellular events and signaling properties induced by Epi or NE in cardiomyocytes. Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. Polyubiquitinated. Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation. Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is oxygen-dependent. Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.

Polymorphism. The Gly-16 allele is overrepresented in individuals affected by nocturnal asthma as compared to controls, and appears to be an important genetic factor in the expression of this asthmatic phenotype.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.

RefSeq proteins (1): NP_000015* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000332	ADRB2_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (97 total): helix 15, binding site 12, mutagenesis site 12, modified residue 10, sequence variant 9, topological domain 8, transmembrane region 7, strand 7, sequence conflict 4, turn 3, lipid moiety-binding region 2, glycosylation site 2, disulfide bond 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

145 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1GQ4	X-RAY DIFFRACTION	1.9
2RH1	X-RAY DIFFRACTION	2.4
6PS2	X-RAY DIFFRACTION	2.4
9RKF	X-RAY DIFFRACTION	2.45
9RKG	X-RAY DIFFRACTION	2.45
5D5A	X-RAY DIFFRACTION	2.48
6PS3	X-RAY DIFFRACTION	2.5
9RKH	X-RAY DIFFRACTION	2.5
6PS4	X-RAY DIFFRACTION	2.6
9RKI	X-RAY DIFFRACTION	2.6
9U4Y	ELECTRON MICROSCOPY	2.67
6PS6	X-RAY DIFFRACTION	2.7
5X7D	X-RAY DIFFRACTION	2.7
9I54	ELECTRON MICROSCOPY	2.72
4LDE	X-RAY DIFFRACTION	2.79
3D4S	X-RAY DIFFRACTION	2.8
6PRZ	X-RAY DIFFRACTION	2.8
9I52	ELECTRON MICROSCOPY	2.8
3NY8	X-RAY DIFFRACTION	2.84
3NY9	X-RAY DIFFRACTION	2.84
9U9V	ELECTRON MICROSCOPY	2.85
8ZWG	ELECTRON MICROSCOPY	2.87
9LW5	ELECTRON MICROSCOPY	2.87
6PS5	X-RAY DIFFRACTION	2.9
8GG0	ELECTRON MICROSCOPY	2.9
9BUY	ELECTRON MICROSCOPY	2.9
6MXT	X-RAY DIFFRACTION	2.96
8GFW	ELECTRON MICROSCOPY	3
8GFX	ELECTRON MICROSCOPY	3
8GFY	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07550-F1	79.74	0.60

Antibody-complex structures (SAbDab): 24 — 2R4R, 2R4S, 3KJ6, 3P0G, 3SN6, 4LDE, 4LDL, 4LDO, 4QKX, 5JQH, 6MXT, 6N48, 6NI3, 7BZ2, 7DHI, 7DHR, 7XK9, 7XKA, 8UHB, 8W1V, 8ZBE, 8ZCJ, 9U4Y, 9U9V

Functional residue map

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

Ligand- & substrate-binding residues (12): 113; 113; 113; 118; 203; 293; 293; 312; 312; 312; 316; 316

Post-translational modifications (12): 141, 246, 261, 262, 345, 346, 355, 356, 382, 395, 265, 341

Disulfide bonds (2): 106–191, 184–190

Glycosylation sites (2): 6, 15

Mutagenesis-validated functional residues (12):

Position	Phenotype
79	affects binding of catecholamines, and produces an uncoupling between the receptor and stimulatory g proteins.
141	abolishes insulin-induced tyrosine phosphorylation and insulin-induced receptor supersensitization.
174	increased noradrenaline affinity.
265	loss of ligand-induced palmitoylation.
300	increased noradrenaline affinity.
341	loss of basal palmitoylation.
341	uncoupled receptor.
345–346	delayed agonist-promoted desensitization.
350	does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
354	does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
366	does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
413	loss of interaction with nherf1 after isoprenaline stimulation. inhibition of slc9a3 activity after isoprenaline stimula

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-390696	Adrenoceptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-5689880	Ub-specific processing proteases
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-162582	Signal Transduction
R-HSA-199991	Membrane Trafficking
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-392499	Metabolism of proteins
R-HSA-500792	GPCR ligand binding
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 515 (showing top): BIOCARTA_GCR_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_COLD, GOBP_CIRCULATORY_SYSTEM_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_RESPONSE_TO_DIETARY_EXCESS, MODULE_64, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT

GO Biological Process (39): diet induced thermogenesis (GO:0002024), norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure (GO:0002025), regulation of sodium ion transport (GO:0002028), transcription by RNA polymerase II (GO:0006366), receptor-mediated endocytosis (GO:0006898), smooth muscle contraction (GO:0006939), cell surface receptor signaling pathway (GO:0007166), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), endosome to lysosome transport (GO:0008333), response to cold (GO:0009409), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of bone mineralization (GO:0030501), heat generation (GO:0031649), negative regulation of multicellular organism growth (GO:0040015), positive regulation of MAPK cascade (GO:0043410), bone resorption (GO:0045453), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of smooth muscle contraction (GO:0045986), brown fat cell differentiation (GO:0050873), positive regulation of mini excitatory postsynaptic potential (GO:0061885), adrenergic receptor signaling pathway (GO:0071875), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), adenylate cyclase-inhibiting adrenergic receptor signaling pathway (GO:0071881), AMPA selective glutamate receptor signaling pathway (GO:0098990), positive regulation of cardiac muscle cell contraction (GO:0106134), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of cAMP/PKA signal transduction (GO:0141163), positive regulation of autophagosome maturation (GO:1901098), positive regulation of lipophagy (GO:1904504), cellular response to amyloid-beta (GO:1904646), response to psychosocial stress (GO:1990911), regulation of systemic arterial blood pressure by norepinephrine-epinephrine (GO:0001993), regulation of smooth muscle contraction (GO:0006940), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), blood vessel diameter maintenance (GO:0097746)

GO Molecular Function (13): amyloid-beta binding (GO:0001540), beta2-adrenergic receptor activity (GO:0004941), adenylate cyclase binding (GO:0008179), potassium channel regulator activity (GO:0015459), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), norepinephrine binding (GO:0051380), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), beta-adrenergic receptor activity (GO:0004939), protein binding (GO:0005515), enzyme binding (GO:0019899)

GO Cellular Component (17): nucleus (GO:0005634), lysosome (GO:0005764), endosome (GO:0005768), early endosome (GO:0005769), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cilium (GO:0005929), endosome membrane (GO:0010008), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), apical plasma membrane (GO:0016324), clathrin-coated endocytic vesicle membrane (GO:0030669), ciliary basal body (GO:0036064), signaling receptor complex (GO:0043235), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), neuronal dense core vesicle (GO:0098992)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Deubiquitination	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cardiac muscle cell apoptotic process	2
regulation of cardiac muscle cell apoptotic process	2
protein binding	2
binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
endosome	2
cellular anatomical structure	2
response to dietary excess	1
adaptive thermogenesis	1
regulation of systemic arterial blood pressure by norepinephrine-epinephrine	1
negative regulation of systemic arterial blood pressure	1
vasodilation	1
sodium ion transport	1
regulation of metal ion transport	1
DNA-templated transcription	1
endocytosis	1
muscle contraction	1
signal transduction	1
adenylate cyclase activity	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
response to stress	1
response to temperature stimulus	1
positive regulation of striated muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
temperature homeostasis	1
multicellular organism growth	1
regulation of multicellular organism growth	1
negative regulation of developmental growth	1
negative regulation of multicellular organismal process	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1

Protein interactions and networks

STRING

2874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRB2	ARRB1	P49407	999
ADRB2	ARRB2	P32121	998
ADRB2	NHERF1	O14745	989
ADRB2	SAG	P10523	984
ADRB2	AKAP12	Q02952	967
ADRB2	SNX27	Q96L92	958
ADRB2	CACNA1C	Q13936	934
ADRB2	GRK2	P25098	913
ADRB2	AKAP5	P24588	877
ADRB2	SRC	P12931	831
ADRB2	TPM3	P06753	822
ADRB2	CXCR4	P30991	819
ADRB2	PRKACA	P17612	813
ADRB2	PRKACG	P22612	811
ADRB2	PRKACB	P22694	811

IntAct

300 interactions, top by confidence:

A	B	Type	Score
ARRDC3	ADRB2	psi-mi:“MI:0403”(colocalization)	0.680
ARRDC3	ADRB2	psi-mi:“MI:0915”(physical association)	0.680
ADRB2	ARRDC3	psi-mi:“MI:0914”(association)	0.680
ADRB2	ADRB2	psi-mi:“MI:2364”(proximity)	0.660
ADRB2	ARRB2	psi-mi:“MI:0915”(physical association)	0.610
ADRB2	GNAS	psi-mi:“MI:0914”(association)	0.610
ADRB2	GNAS	psi-mi:“MI:0915”(physical association)	0.610
ADRB2	ADORA1	psi-mi:“MI:0915”(physical association)	0.610
ADORA1	ADRB2	psi-mi:“MI:0914”(association)	0.610
EZH2	ADRB2	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	ELL2	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	SNW1	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	BRPF3	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	RNF138	psi-mi:“MI:0915”(physical association)	0.560
BRWD1	ADRB2	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	PARP11	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	E2F8	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	RNF208	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	TEX35	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	EEF1DP3	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	TMEM61	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (424): ARRDC3 (Affinity Capture-Western), ADRB2 (Affinity Capture-Western), ADRB2 (Affinity Capture-Western), ADRB2 (Affinity Capture-Western), HGS (Affinity Capture-Western), CLTC (Affinity Capture-Western), ADRB2 (Affinity Capture-Western), USP20 (Affinity Capture-Western), MAP1LC3B (Affinity Capture-Western), GNAS (Affinity Capture-Western), ARRDC3 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), ARRDC3 (FRET), ARRB2 (FRET), ARRDC3 (Reconstituted Complex)

ESM2 similar proteins: A0A678XMK4, A6QLE7, G3M4F8, O08890, O42384, O42574, O70528, P07550, P0C5J4, P10608, P17124, P18762, P25021, P25102, P28221, P28222, P28334, P28564, P28565, P28566, P30939, P30940, P35404, P35406, P46636, P47747, P56496, P60020, P60021, P61752, P79748, P97288, Q02284, Q0EAB5, Q13639, Q28044, Q28509, Q588Y6, Q61224, Q62758

Diamond homologs: G3M4F8, O02662, O02666, O02824, O08890, O42384, O42385, O42574, O70528, O77680, P04274, P07550, P07700, P08908, P10608, P15823, P17124, P18090, P18130, P18762, P18841, P18901, P19327, P21728, P21918, P23944, P25021, P25100, P25102, P25115, P25962, P26255, P28565, P30939, P32304, P32305, P34969, P35348, P35368, P35406

SIGNOR signaling

49 interactions.

A	Effect	B	Mechanism
AKT	down-regulates	ADRB2	phosphorylation
(R)-adrenaline	up-regulates	ADRB2	“chemical activation”
“albuterol sulfate”	up-regulates	ADRB2	“chemical activation”
AKT1	down-regulates	ADRB2	phosphorylation
ADRB2	“up-regulates activity”	GNAS	binding
ADRB2	“up-regulates activity”	GNAL	binding
ADRB2	“up-regulates activity”	GNAQ	binding
ADRB2	“up-regulates activity”	GNA14	binding
L-isoprenaline	“up-regulates activity”	ADRB2	“chemical activation”
(R)-salbutamol	“up-regulates activity”	ADRB2	“chemical activation”
EGLN3	“up-regulates quantity by stabilization”	ADRB2	hydroxylation
PRKCD	“down-regulates activity”	ADRB2	phosphorylation
GRK5	unknown	ADRB2	phosphorylation
INSR	“down-regulates activity”	ADRB2	phosphorylation
ARRB2	“down-regulates activity”	ADRB2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
Assembly and cell surface presentation of NMDA receptors	6	16.6×	3e-04
Neurexins and neuroligins	7	15.0×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	5	25.5×	4e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	5	21.7×	7e-04
chemical synaptic transmission	11	7.5×	1e-04
protein transport	12	4.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	7
Benign	23

Top pathogenic / likely-pathogenic (0)

SpliceAI

30 predictions. Top by Δscore:

Variant	Effect	Δscore
5:148826965:T:TA	acceptor_gain	0.7500
5:148826982:A:AG	acceptor_gain	0.6300
5:148826978:T:TA	acceptor_gain	0.4300
5:148827144:T:TA	acceptor_gain	0.3800
5:148826982:AAT:A	acceptor_gain	0.3700
5:148827336:A:T	acceptor_gain	0.3700
5:148826982:AATGT:A	acceptor_gain	0.2900
5:148827337:T:TT	acceptor_gain	0.2800
5:148827338:T:TT	acceptor_gain	0.2800
5:148827341:GAT:G	acceptor_gain	0.2700
5:148827055:T:A	acceptor_gain	0.2600
5:148827332:G:T	acceptor_gain	0.2600
5:148827346:ACT:A	acceptor_gain	0.2500
5:148826989:T:A	acceptor_gain	0.2300
5:148827331:T:TA	acceptor_loss	0.2300
5:148827336:ATTC:A	acceptor_loss	0.2300
5:148827337:TTCA:T	acceptor_loss	0.2300
5:148827338:TCA:T	acceptor_loss	0.2300
5:148827339:CA:C	acceptor_loss	0.2300
5:148827340:A:AC	acceptor_loss	0.2300
5:148827341:G:A	acceptor_loss	0.2300
5:148827747:G:GT	donor_gain	0.2300
5:148827138:A:AG	acceptor_gain	0.2200
5:148827326:CTTCT:C	acceptor_loss	0.2200
5:148827327:TTCTT:T	acceptor_loss	0.2200
5:148827369:G:GT	acceptor_loss	0.2200
5:148826986:T:TA	acceptor_gain	0.2100
5:148827325:C:CT	acceptor_gain	0.2100
5:148827325:CCTT:C	acceptor_loss	0.2000
5:148827328:TCTT:T	acceptor_loss	0.2000

AlphaMissense

2740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:148826984:T:A	N51K	1.000
5:148826984:T:G	N51K	1.000
5:148827189:A:C	S120R	1.000
5:148827191:C:A	S120R	1.000
5:148827191:C:G	S120R	1.000
5:148827223:G:C	R131P	1.000
5:148827303:T:A	W158R	1.000
5:148827303:T:C	W158R	1.000
5:148827675:T:C	F282L	1.000
5:148827677:C:A	F282L	1.000
5:148827677:C:G	F282L	1.000
5:148827055:T:C	L75P	0.999
5:148827058:C:A	A76D	0.999
5:148827066:G:C	D79H	0.999
5:148827067:A:C	D79A	0.999
5:148827067:A:G	D79G	0.999
5:148827067:A:T	D79V	0.999
5:148827068:T:A	D79E	0.999
5:148827068:T:G	D79E	0.999
5:148827070:T:C	L80P	0.999
5:148827078:G:C	G83R	0.999
5:148827128:G:C	W99C	0.999
5:148827128:G:T	W99C	0.999
5:148827147:T:A	C106S	0.999
5:148827148:G:C	C106S	0.999
5:148827186:G:C	A119P	0.999
5:148827202:T:C	L124P	0.999
5:148827213:G:C	A128P	0.999
5:148827214:C:A	A128E	0.999
5:148827453:T:C	F208L	0.999

dbSNP variants (sampled 300 via entrez): RS1000413676 (5:148825750 C>A,T), RS1001319675 (5:148826349 G>A,C,T), RS1001584128 (5:148826109 G>A,C,T), RS1002293877 (5:148826087 T>A), RS1002429653 (5:148826334 G>A), RS1003435946 (5:148824895 T>C), RS1004071882 (5:148827575 G>A), RS1004856855 (5:148825149 G>A,C), RS1005525661 (5:148828470 G>T), RS1005565168 (5:148827637 A>T), RS1005867211 (5:148826533 C>A,T), RS1005899777 (5:148826391 G>A), RS1008147293 (5:148826595 A>C,G,T), RS1009129406 (5:148828396 G>A,C), RS1009149625 (5:148825462 C>T)

Disease associations

OMIM: gene MIM:109690 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited susceptibility to asthma	Limited	Autosomal dominant

Mondo (1): inherited susceptibility to asthma (MONDO:0010940)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004632_114	Lymphocyte percentage of white cells	4.000000e-13
GCST005777_2	Systolic blood pressure	9.000000e-06
GCST007430_33	Peak expiratory flow	2.000000e-16
GCST007431_47	Lung function (FEV1/FVC)	2.000000e-27
GCST007432_67	FEV1	6.000000e-18
GCST007692_45	Chronic obstructive pulmonary disease	3.000000e-07
GCST011766_6	Chronic obstructive pulmonary disease	9.000000e-13
GCST90002382_131	Eosinophil percentage of white cells	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0006335	systolic blood pressure
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094118 (PROTEIN FAMILY), CHEMBL2096974 (SELECTIVITY GROUP), CHEMBL210 (SINGLE PROTEIN), CHEMBL2111388 (SELECTIVITY GROUP), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

166 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 523,969 (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
CHEMBL1200323	LABETALOL HYDROCHLORIDE	4	2,621
CHEMBL1215	PHENYLEPHRINE	4	37,782
CHEMBL1437	NOREPINEPHRINE	4	108,675
CHEMBL1671	PROPRANOLOL HYDROCHLORIDE	4	21,811
CHEMBL1700	SOTALOL HYDROCHLORIDE	4	3,968
CHEMBL27	PROPRANOLOL	4	85,886
CHEMBL434	ISOPROTERENOL	4	40,234
CHEMBL471	SOTALOL	4	21,777
CHEMBL6995	PRACTOLOL	4	4,261
CHEMBL1002	LEVOSALBUTAMOL	4	27,028
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1095777	INDACATEROL	4	2,735
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL1198857	VILANTEROL	4	2,552
CHEMBL1200438	TIOCONAZOLE	4	15,162
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1200833	DIPIVEFRIN HYDROCHLORIDE	4
CHEMBL1201153	ISOETHARINE MESYLATE	4
CHEMBL1201213	ISOETHARINE	4
CHEMBL1201237	LEVOBUNOLOL	4
CHEMBL1201794	RIBOFLAVIN 5’-PHOSPHATE	4
CHEMBL1256786	FORMOTEROL	4
CHEMBL1256958	EPINEPHRINE BITARTRATE	4
CHEMBL1263	SALMETEROL	4
CHEMBL1276308	MIFEPRISTONE	4
CHEMBL13	METOPROLOL	4

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

PharmGKB clinical annotations

23 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1042713	Efficacy	2A	salmeterol	Asthma
rs1042713	Efficacy	3	corticosteroids	Asthma
rs1042713	Efficacy	3	corticosteroids;selective beta-2-adrenoreceptor agonists	Asthma
rs1042713	PD	3	salbutamol
rs1042713	Efficacy	3	salbutamol	Asthma
rs1042713	Efficacy	4	benazepril	Essential hypertension
rs1042713	Efficacy	4	Beta Blocking Agents	Cardiomyopathy;Dilated;Heart Failure
rs1042713	Toxicity	3	risperidone	Schizophrenia
rs1042713	Efficacy	3	methacholine	Asthma
rs1042713	Efficacy	3	tiotropium	Asthma
rs1042713	Other	3	isoproterenol
rs1042713	Efficacy	3	Ace Inhibitors;Plain;Angiotensin II Antagonists;Beta Blocking Agents;digoxin;diuretics;spironolactone	Heart Failure
rs1042713	Dosage	3	ephedrine;phenylephrine
rs1042713	Efficacy	3	propranolol	Liver Cirrhosis
rs1042713	Efficacy	3	atenolol;metoprolol	Tachycardia
rs1042714	Efficacy	3	enalapril	Hypertrophy;Left Ventricular
rs1042714	Efficacy	3	carvedilol	Heart Failure
rs1042714	Efficacy	3	terbutaline
rs1042714	Toxicity	3	atenolol;metoprolol	Hypertension
rs1042714	Efficacy	3	atenolol;metoprolol	Tachycardia
rs1042718	Toxicity	3	fentanyl;propofol;remifentanil;sevoflurane	Hypotensive disorder
rs1042718	Other	3	fentanyl
rs1800888	Other	3	salbutamol

PharmGKB variants

10 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1042711	ADRB2		0.00	0
rs1042713	ADRB2	2A	11.75	15	salmeterol;salbutamol;corticosteroids;corticosteroids;selective beta-2-adrenoreceptor agonists;methacholine;benazepril;risperidone;isoproterenol;tiotropium;ephedrine;phenylephrine
rs1042714	ADRB2	3	5.25	5	enalapril;carvedilol;atenolol;metoprolol;terbutaline
rs1800888	ADRB2	3	0.00	1	salbutamol
rs2053044	ADRB2		0.00	0
rs2400707	ADRB2		0.00	0
rs11959113	ADRB2	3	2.25	1	fentanyl
rs1042718	ADRB2	3	3.00	2	fentanyl;fentanyl;propofol;remifentanil;sevoflurane
rs1042719	ADRB2		0.00	0
rs1042717	ADRB2		0.00	0

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	carvedilol;labetalol;nadolol;pindolol;propranolol;sotalol	Annotation of CPIC Guideline for carvedilol, labetalol, nadolol, pindolol, propranolol, sotalol and ADRB2

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (54 total), top 25:

Ligand	Action	Affinity	Parameter
CHF-6366	Agonist	11.4	pKd
[125I]ICYP	Antagonist	11.4	pKd
carvedilol	Antagonist	10.6	pKi
carazolol	Antagonist	10.5	pKi
7-methylcyanopindolol	Inverse agonist	10.4	pKd
[3H]dihydroalprenolol	Antagonist	10.1	pKd
formoterol	Agonist	10.08	pEC50
BI-167107	Agonist	10.0	pEC50
olodaterol	Agonist	10.0	pEC50
bupranolol	Antagonist	9.9	pKi
salmeterol	Partial agonist	9.9	pEC50
[3H]CGP12177	Partial agonist	9.8	pKd
timolol	Antagonist	9.7	pKi
propranolol	Antagonist	9.5	pKi
CGP 12177	Antagonist	9.4	pKi
ICI 118551	Inverse agonist	9.4	pKi
vilanterol	Agonist	9.4	pEC50
pindolol	Partial agonist	9.4	pKi
SR59230A	Antagonist	9.3	pKi
bunolol	Antagonist	9.26	pKi
abediterol	Full agonist	9.22	pIC50
clenbuterol	Agonist	9.2	pEC50
alprenolol	Partial agonist	9.0	pKi
fenoterol	Agonist	8.9	pEC50
nadolol	Antagonist	8.6	pKi

Binding affinities (BindingDB)

337 measured of 367 human assays (435 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(-)ISOPROTERENOL	IC50	0.05 nM	US-9492405: Use of fenoterol and fenoterol analogues in the treatment of glioblastomas and astrocytomas
N-adamantan-1-yl-2-(3-{(R)-2-[(R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetamide	EC50	0.06 nM
[1-[3-[4-[2-[3-[(1R)-1-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]ethyl]phenyl]ethylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[4-[2-[[4-[2-[2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethylamino]propyl]phenyl]methylamino]-2-oxoethyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
roxindole	KI	0.11 nM
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]urea	KI	0.15 nM
[1-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]methyl]-5-methoxy-2-methylphenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.2 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[4-[2-[[(2R)-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)propyl]amino]propyl]phenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.3 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[4-[2-[[2-chloro-4-[[[(2R)-2-hydroxy-2-(5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]methyl]-5-methoxyphenyl]carbamoyloxy]ethyl-methylamino]cyclohexyl] 2-hydroxy-2,2-dithiophen-2-ylacetate	IC50	0.38 nM	US-9315463: Cyclohexylamine derivatives having β2 adrenergic agonist and M3 muscarinic antagonist activities
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
NSC_112184	KI	0.5 nM
4-[3-(tert-butylamino)-2-hydroxypropoxy]-2,3-dihydro-1H-1,3-benzodiazol-2-one hydrochloride	KD	0.62 nM
[1-[3-[[4-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methylanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[4-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methoxyanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[4-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2,5-dimethylanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[4-[2-chloro-4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-5-methoxyanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[4-[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]anilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[2-[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]acetyl]amino]propyl-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]acetyl]amino]propyl-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[5-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methylanilino]-5-oxopentyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[5-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methoxyanilino]-5-oxopentyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[5-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-3-methoxyanilino]-5-oxopentyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[5-[2-chloro-4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-5-methoxyanilino]-5-oxopentyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[5-[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]ethyl]anilino]-5-oxopentyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[5-[4-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]ethyl]anilino]-5-oxopentyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[4-[[2-[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]acetyl]amino]butyl-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[4-[[2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]acetyl]amino]butyl-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[4-[[2-[3-[(2S)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]acetyl]amino]butyl-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]phenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methylphenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methylphenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methoxyphenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2,5-dimethylphenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[2-chloro-4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-5-methoxyphenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9682957: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[3-[[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]ethyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]ethyl]phenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]ethyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9682957: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[3-[[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[3-[(2R)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[3-[(2S)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[4-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9682957: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[(2R)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[(2S)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]methylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[3-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]methylcarbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]methylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[(2R)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]methylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[4-[(2S)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]phenyl]methylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity

ChEMBL bioactivities

3382 potent at pChembl≥5 of 3627 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.97	EC50	0.01072	nM	CHEMBL4847536
10.94	EC50	0.01148	nM	CHEMBL5570917
10.92	Ki	0.012	nM	CHEMBL2012522
10.90	Ki	0.01259	nM	CHEMBL4871517
10.90	EC50	0.01259	nM	CHEMBL4871708
10.90	Ki	0.01259	nM	CHEMBL5550055
10.90	Ki	0.01259	nM	CHEMBL5517637
10.90	Ki	0.01259	nM	CHEMBL6067690
10.89	EC50	0.01288	nM	CHEMBL4873082
10.88	EC50	0.01318	nM	CHEMBL5574011
10.88	EC50	0.01318	nM	CHEMBL5571865
10.87	EC50	0.01349	nM	CHEMBL4848793
10.83	EC50	0.01479	nM	CHEMBL4854569
10.80	Ki	0.01585	nM	CHEMBL4863525
10.80	Ki	0.01585	nM	CHEMBL5505762
10.80	Ki	0.01585	nM	CHEMBL5555464
10.80	Ki	0.01585	nM	CHEMBL5559271
10.80	EC50	0.01585	nM	CHEMBL5571445
10.79	EC50	0.01622	nM	CHEMBL4634131
10.78	EC50	0.0166	nM	CHEMBL4865710
10.76	EC50	0.01738	nM	CHEMBL4848018
10.75	EC50	0.01778	nM	CHEMBL4848704
10.75	EC50	0.01778	nM	CHEMBL4862449
10.74	Kd	0.0182	nM	CHEMBL4092412
10.74	EC50	0.0182	nM	CHEMBL4860454
10.74	EC50	0.0182	nM	CHEMBL4868938
10.74	EC50	0.0182	nM	CHEMBL4854261
10.71	EC50	0.0195	nM	CHEMBL4855974
10.70	EC50	0.02	nM	CHEMBL230486
10.70	EC50	0.02	nM	CHEMBL236039
10.70	EC50	0.02	nM	OLODATEROL
10.70	Ki	0.01995	nM	CHEMBL5184455
10.70	Ki	0.01995	nM	CHEMBL5558368
10.70	Ki	0.01995	nM	CHEMBL5558825
10.70	EC50	0.02	nM	CHEMBL1242943
10.68	EC50	0.021	nM	CHEMBL4445289
10.68	EC50	0.02089	nM	CHEMBL4445289
10.67	EC50	0.02138	nM	CHEMBL4872480
10.67	EC50	0.02138	nM	CHEMBL4863282
10.66	EC50	0.022	nM	CHEMBL236041
10.65	EC50	0.02239	nM	CHEMBL4857267
10.65	EC50	0.02239	nM	CHEMBL4868585
10.65	EC50	0.02239	nM	CHEMBL5573592
10.65	EC50	0.02239	nM	CHEMBL5574770
10.64	EC50	0.023	nM	CHEMBL1243189
10.63	EC50	0.02344	nM	CHEMBL4868684
10.62	EC50	0.02399	nM	CHEMBL4635163
10.62	EC50	0.02399	nM	CHEMBL5565495
10.62	EC50	0.024	nM	CHEMBL230490
10.61	EC50	0.02455	nM	CHEMBL4846631

PubChem BioAssay actives

2188 with measured affinity, of 6100 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
5-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]-N-(pyridin-2-ylmethyl)-1H-indole-2-carboxamide	302101: Agonist activity at human recombinant adrenergic beta-2 receptor expressed in CHO cells assessed as elevation in cAMP levels	ec50	<0.0001	uM
5-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]-N-(1,3-thiazol-2-ylmethyl)-1H-indole-2-carboxamide	302101: Agonist activity at human recombinant adrenergic beta-2 receptor expressed in CHO cells assessed as elevation in cAMP levels	ec50	<0.0001	uM
N-[(3,4-dichlorophenyl)methyl]-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-benzyl-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-benzyl-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	290780: Agonist activity at human recombinant beta-2 adrenoceptor expressed in CHO cells assessed as elevation of cAMP	ec50	<0.0001	uM
2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]-N-(2-phenylethyl)acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-[(2-ethoxyphenyl)methyl]-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-benzyl-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-(cyclohexylmethyl)-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]-N-(3-phenylpropyl)acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]-N-[(2-methoxyphenyl)methyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
Olodaterol	1760531: Agonist activity at beta2 adrenoceptor (unknown origin)	ec50	<0.0001	uM
N-[(2-chloro-4-hydroxyphenyl)methyl]-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-[(4-hydroxy-2,6-dimethylphenyl)methyl]-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
Olodaterol Hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[[4-[3-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propylcarbamoyl]phenyl]methoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl (2R)-2-hydroxy-2-[3-[[4-[3-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propylcarbamoyl]phenyl]methoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-cyclobutylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]benzoyl]amino]propoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-methylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]benzoyl]amino]propoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl 1-[[5-[4-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]butylcarbamoyl]thiophen-2-yl]methylamino]-2,3-dihydroindene-1-carboxylate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-4H-1,4-benzoxazin-3-one	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
4-[3-(tert-butylamino)-2-hydroxypropoxy]-1H-indole-2-carbonitrile	1626022: Displacement of [3H]DHA from inactive/G protein-uncoupled human beta2-AR expressed in CHO cell membranes by liquid scintillation counting	kd	<0.0001	uM
8-hydroxy-5-[(1R)-1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(3-hydroxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(2-methoxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(2-hydroxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(3-methoxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(3-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(3-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(2-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(3-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(2-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(4-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(4-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(3-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(4-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(4-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
butanedioic acid;6-[4-[2-[[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide	652454: Displacement of [125I]Iodocyanopindolol from human adrenergic beta2 receptor expressed in insect sf9 cells by scintillation counting	ki	<0.0001	uM
5-[2-[3-(3-fluorophenyl)propylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[[2-methyl-4-(3-methylphenyl)butan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[[4-(3-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[4-(4-methoxyphenyl)butan-2-ylamino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-4-(2-methoxyphenyl)butan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
5-[2-[4-(4-chlorophenyl)butan-2-ylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
5-[2-[[4-(3-chlorophenyl)-2-methylbutan-2-yl]amino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
5-[2-[4-(2-chlorophenyl)butan-2-ylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[4-(2-methoxyphenyl)butan-2-ylamino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[[4-(2-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Terbutaline	increases abundance, increases phosphorylation, affects reaction, affects response to substance, increases expression (+10 more)	23
Carvedilol	affects binding, decreases activity, increases expression, decreases reaction, increases activity (+7 more)	15
ICI 118551	decreases reaction, decreases response to substance, affects cotreatment, increases activity, decreases activity (+7 more)	14
Isoproterenol	increases uptake, decreases response to substance, increases activity, increases reaction, increases abundance (+6 more)	14
Cyclic AMP	increases reaction, increases abundance, affects abundance, decreases abundance, decreases reaction (+5 more)	11
Propranolol	affects binding, decreases abundance, affects cotreatment, decreases reaction, increases activity (+6 more)	11
Albuterol	increases phosphorylation, decreases response to substance, affects binding, increases activity, decreases abundance (+3 more)	10
Epinephrine	decreases reaction, increases activity, affects binding, increases abundance, increases phosphorylation (+2 more)	7
Valproic Acid	increases expression, affects expression, affects cotreatment	7
Salmeterol Xinafoate	increases expression, increases activity, increases abundance, increases phosphorylation, decreases reaction (+2 more)	6
Formoterol Fumarate	decreases reaction, affects binding, increases activity, increases abundance, increases expression (+3 more)	5
Fenoterol	increases abundance, increases phosphorylation, decreases reaction, affects binding, increases activity (+1 more)	5
Particulate Matter	increases expression, increases abundance, affects cotreatment, increases phosphorylation, increases methylation (+3 more)	5
Atenolol	decreases abundance, decreases reaction, increases activity, increases expression, affects binding (+3 more)	4
CGP 12177	affects binding, decreases reaction, decreases activity, decreases abundance	3
Alprenolol	affects binding, increases abundance, increases phosphorylation, affects cotreatment, increases expression (+1 more)	3
Cisplatin	affects cotreatment, increases expression	3
Dactinomycin	affects cotreatment, increases expression, decreases reaction, affects expression	3
Colforsin	affects cotreatment, increases abundance, increases reaction, increases activity, affects reaction (+4 more)	3
Metoprolol	decreases activity, decreases reaction, affects response to substance, affects binding, decreases abundance	3
Norepinephrine	affects binding, increases activity, increases abundance, decreases reaction	3
Metaproterenol	increases phosphorylation, affects expression, affects binding, increases activity, increases abundance (+1 more)	3
Pindolol	decreases reaction, decreases expression, affects binding, increases abundance, increases phosphorylation (+2 more)	3
Potassium	affects binding, decreases abundance, increases activity, affects cotreatment, affects reaction (+2 more)	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
trichostatin A	affects expression, increases expression	2
sodium arsenite	decreases expression	2
broxaterol	affects binding, increases activity, increases abundance, decreases reaction	2

ChEMBL screening assays

1026 unique, capped per target: 596 binding, 423 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3254788	Binding	Inhibition of beta-adrenergic receptor (unknown origin)	Linked Aryl Aryloxypropanolamines as a new class of lipid catabolis agents. — J Med Chem
CHEMBL646912	Functional	In vitro agonistic activity against cAMP accumulation level in CHO cells expressing human beta-AR receptor	4-Aminopiperidine ureas as potent selective agonists of the human beta(3)-adrenergic receptor. — Bioorg Med Chem Lett
CHEMBL4051050	ADMET	Agonist activity at recombinant human beta2 adrenergic receptor expressed in CHO cells assessed as accumulation of cyclic AMP after 30 mins	Discovery of Novel Indazole Derivatives as Orally Available β3-Adrenergic Receptor Agonists Lacking Off-Target-Based Cardiovascular Side Effects. — J Med Chem

Cellosaurus cell lines

22 cell lines: 8 transformed cell line, 7 cancer cell line, 5 spontaneously immortalized cell line, 1 telomerase immortalized cell line, 1 hybrid cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6631	Gbeta2AR13	Transformed cell line	Female
CVCL_9869	HEK-293B2	Transformed cell line	Female
CVCL_B1BR	Abcam A-431 ADRB2 KO	Cancer cell line	Female
CVCL_B8B1	Abcam HCT 116 ADRB2 KO	Cancer cell line	Male
CVCL_B8S7	Abcam MCF-7 ADRB2 KO	Cancer cell line	Female
CVCL_B9D3	Abcam A-549 ADRB2 KO	Cancer cell line	Male
CVCL_C0S5	ACTOne ADRB2	Transformed cell line	Female
CVCL_C3K0	N/Tert-1 ADRB2	Telomerase immortalized cell line	Male
CVCL_D7JS	Ubigene A-549 ADRB2 KO	Cancer cell line	Male
CVCL_D9XA	Ubigene HeLa ADRB2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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