ADRA1B

Summary

ADRA1B (adrenoceptor alpha 1B, HGNC:278) is a protein-coding gene on chromosome 5q33.3, encoding Alpha-1B adrenergic receptor (P35368). Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11).

Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region.

Source: NCBI Gene 147 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 95 total
• Druggable target: yes — 84 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:278
Approved symbol	ADRA1B
Name	adrenoceptor alpha 1B
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170214
Ensembl biotype	protein_coding
OMIM	104220
Entrez	147

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000306675, ENST00000641205, ENST00000641475, ENST00000865014

RefSeq mRNA: 1 — MANE Select: NM_000679 NM_000679

CCDS: CCDS4347

Canonical transcript exons

ENST00000306675 — 2 exons

Exon	Start	End
ENSE00001162336	159916482	159917854
ENSE00001210301	159971879	159973012

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 84.33.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7278 / max 279.8528, expressed in 680 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59878	2.1046	638
59879	0.4594	156
59875	0.0634	10
59876	0.0519	9
59880	0.0485	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	84.33	gold quality
thoracic aorta	UBERON:0001515	84.28	gold quality
ascending aorta	UBERON:0001496	84.27	gold quality
descending thoracic aorta	UBERON:0002345	82.04	gold quality
aorta	UBERON:0000947	80.67	gold quality
popliteal artery	UBERON:0002250	78.37	gold quality
tibial artery	UBERON:0007610	78.33	gold quality
prefrontal cortex	UBERON:0000451	78.28	gold quality
cingulate cortex	UBERON:0003027	76.07	gold quality
anterior cingulate cortex	UBERON:0009835	75.89	gold quality
right lung	UBERON:0002167	75.70	gold quality
right frontal lobe	UBERON:0002810	75.18	gold quality
spleen	UBERON:0002106	74.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.16	gold quality
liver	UBERON:0002107	71.54	gold quality
omental fat pad	UBERON:0010414	70.64	gold quality
peritoneum	UBERON:0002358	70.55	gold quality
neocortex	UBERON:0001950	70.41	gold quality
frontal cortex	UBERON:0001870	70.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	69.00	gold quality
left uterine tube	UBERON:0001303	68.56	gold quality
upper lobe of left lung	UBERON:0008952	67.13	gold quality
apex of heart	UBERON:0002098	67.01	gold quality
stromal cell of endometrium	CL:0002255	66.98	gold quality
amygdala	UBERON:0001876	66.26	gold quality
left coronary artery	UBERON:0001626	66.05	gold quality
right ovary	UBERON:0002118	66.05	gold quality
right atrium auricular region	UBERON:0006631	65.70	gold quality
cerebral cortex	UBERON:0000956	65.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXD2, SP1

miRNA regulators (miRDB)

24 targeting ADRA1B, 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-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-4749-3P	96.40	66.24	798

Literature-anchored findings (GeneRIF, showing 40)

• Data show thah activation of alpha(1)A- or alpha(1)B-adrenergic receptors inhibits serum-promoted cell proliferation, whereas alpha(1)D-AR activation does not show such an inhibitory effect. (PMID:12409310)
• the alpha(1B)-AR has differential effects on the phosphorylation status of the STAT3 pathway and may not be as prohypertrophic as the other two subtypes. (PMID:12695539)
• These studies suggest that gC1qR interacts specifically with alpha1B- and alpha1D-, but not alpha1A-ARs, and this interaction depends on the presence of an intact C-tail. (PMID:14626446)
• heterodimerization with alpha1B-adrenergic receptors controls cell surface expression of alpha1D-adrenergic receptors (PMID:14736874)
• the alpha(1B)-adrenoreceptor has a role in the inhibition of migration of human aortic smooth muscle cells (PMID:15220331)
• alpha(1B)-adrenergic receptor expression causes a cell cycle progression and may induce transformation in sensitive cell lines. (PMID:15297446)
• Human ureter was endowed with each alpha1 AR subtype, although alpha1D and alpha1A ARs were prevalent over alpha1B ARs (PMID:15690361)
• These results indicate that the thio-acylation status of the alpha1b-adrenoceptor does not regulate G protein activation whereas thio-acylation of Galpha11 plays a key role in activation by the receptor. (PMID:16297597)
• Ezrin directly interacts with the alpha1b-adrenergic receptor and plays a role in receptor recycling. (PMID:16352594)
• the ADRA1B is able to form oligomeric rather than only simple dimeric complexes and disruption of effective oligomerization by introducing mutations into transmembrane domain IV has profound consequences for cell surface delivery and function (PMID:17220353)
• alpha1B-ARs are the major alpha1-AR subtype expressed in DU145, PC3, and all TRAMP cell lines, but most of the receptor is localized in intracellular compartments in a nonfunctional state, which can be rescued upon prolonged incubation with any ligand. (PMID:17365508)
• In the proximal and medial ureter, the distribution of ARs was alpha 1d > or = alpha 1a > alpha 1b; In the distal ureter, the distribution of ARs was alpha 1d > alpha 1a > alpha 1b (PMID:17681068)
• expression in distal ureter significantly higher than in proximal and mid ureter (PMID:17973108)
• ADRA1B expression was increased in end stage renal disease. Functional receptor changes mediated vascular hypersensitivity to phenylephrine. (PMID:18257748)
• Pharmacological profile of alpha 1B-adrenoceptors for ketanserin is strongly influenced by the assay conditions. (PMID:18336813)
• These findings demonstrate differences in internalization between the alpha1a- and alpha1b-AR and provide evidence that the lack of significant endocytosis of the alpha1a-AR is linked to its poor interaction with beta-arrestins as well as with AP50. (PMID:18523139)
• Functional alpha1- and beta2-adrenergic receptors in human osteoblasts. (PMID:19334040)
• Report alpha1A and alpha1B subtypes are both present in human myocardium, but alpha1D binding is not, and the alpha1 subtypes are not downregulated in heart failure. (PMID:19919991)
• These results are the first to demonstrate alpha1-ARs on human coronary ECs and indicate that the alpha1B subtype is predominant. (PMID:20857090)
• The mRNA expression of alpha1b-AR subtypes in bladder detrusor and posterior urethra was significantly lower in the inflammation group than in controls. (PMID:21223784)
• A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling complex involved in alpha1-adrenergic receptor-induced p38 activation. (PMID:21224381)
• alpha1b and alpha2c AR is over-expressed in basal-like breast tumours of poor prognosis (PMID:21298476)
• Data show that sphingosine 1-phosphate can induce alpha1B-adrenergic receptor internalization and that its autocrine/paracrine generation is relevant for internalization induced by IGF-I. (PMID:22019450)
• Through beta-D receptor heteromers dopamine inhibits adrenergic receptor signaling and blocks the synthesis of melatonin induced by adrenergic receptor ligands. (PMID:22723743)
• A rare ADRA1B haplotype composed of six single nucleotide polymorphism(SNP)s is associated with attention deficit hyperactivity disorder (ADHD). (PMID:23052569)
• Noradrenaline facilitated cell proliferation by regulation of potassium currents in human osteoblasts via G(i/o) -protein-coupled alpha(1B) -adrenoceptors, not via coupling to Gq-proteins (PMID:23061915)
• alpha1B-AR signals through calcium, ERK1/2 and p38 only when located in the membrane and the signals disappear by membrane disruption. (PMID:23717684)
• Mean alpha-receptor stain rates in renal pelvis were 2.65 +/- 0.74, 1.35 +/- 0.81 and 2.9 +/- 0.30 for alpha 1A, 1B and 1D, respectively. For calyces, the rates are 2.40 +/- 0.82, 1.50 +/- 0.76 and 2.75 +/- 0.44 for alpha 1A, 1B and 1D, respectively. (PMID:23877383)
• alpha1A-adrenergic receptors are stably expressed and stimulate cell migration and TGF-beta1, IGF-1, hyaluronan and PIP production in human skin fibroblasts. (PMID:24844469)
• heteromeric receptor complexes between alpha1A-AR and CXCR4 and between alpha1B-AR and CXCR4 are constitutively expressed in rat and human vascular smooth muscle cells; the quaternary structure of the receptor complex is important for signaling and contraction (PMID:25775528)
• eIF3f/alpha adrenergic receptor interaction (PMID:26497985)
• ADRA1B rs10070745 was significantly associated with vasoconstrictor responses. (PMID:27089938)
• Receptor Species-dependent Desensitization Controls KCNQ1/KCNE1 K+ Channels as Downstream Effectors of Gq Protein-coupled Receptors.( (PMID:27834678)
• protein kinase C modulates alpha1B-adrenergic receptor transfer to late endosomes and that Rab9 regulates this process and participates in G protein-mediated signaling turn-off. (PMID:28082304)
• Hetero-oligomerization of a1B/D-adrenergic receptor with the chemokine (C-X-C motif) receptor 4:atypical chemokine receptor 3 heteromeric complex is required for a1B/Dadrenergic receptor function. (PMID:28862946)
• ADRA1 expression was greater on vascular smooth muscle in burn scars than in unscarred tissue, and greater on dermal nerve fibres, blood vessels and fibroblasts in keloid scars than in either burn scars or unscarred skin. (PMID:29089212)
• The association of variants in the ADRA1B gene with psoriasis could explain why variants in the IL-12B, ADRA1B and PTTG1 gene regions are associated with psoriasis. (PMID:30785334)
• Mutations in the NPxxY motif stabilize pharmacologically distinct conformational states of the alpha1B- and beta2-adrenoceptors. (PMID:30862702)
• Tumor necrosis factor alpha induces alpha1B-adrenergic receptor expression in keratinocytes. (PMID:31520851)
• Study data indicate that GRK2 and RAB5 play key roles in alpha1B-adrenergic receptor phosphorylation, internalization, and desensitization. The possibility that RAB5 might form part of a signaling complex is suggested, as well as that GDP-Rab5 might interfere with the ability of GRK2 to catalyze alpha1B-adrenergic receptor phosphorylation. (PMID:31811856)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adra1ba	ENSDARG00000011317
danio_rerio	adra1bb	ENSDARG00000041173
mus_musculus	Adra1b	ENSMUSG00000050541
rattus_norvegicus	Adra1b	ENSRNOG00000060087
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), ADRA1A (ENSG00000120907), DRD2 (ENSG00000149295), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRB2 (ENSG00000169252), 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

Alpha-1B adrenergic receptor — P35368 (reviewed: P35368)

Alternative names: Alpha-1B adrenoreceptor

All UniProt accessions (2): P35368, A0A286YF88

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C. ADRA1B binds the catecholamine ligands norepinephrine and epinephrine. Can also couple to G(14) and G(16) proteins. Nuclear ADRA1B forms heterooligomers with ADRA1A to regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. At the plasma membrane, ADRA1B interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy.

Subunit / interactions. Homo- and heterooligomer. Heterooligomerizes with ADRA1A homooligomers in cardiac myocytes. Interacts with CAVIN4.

Subcellular location. Nucleus membrane. Cell membrane. Cytoplasm. Membrane. Caveola.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1B sub-subfamily.

RefSeq proteins (1): NP_000670* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001115	ADRA1B_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (32 total): topological domain 8, transmembrane region 7, glycosylation site 4, region of interest 2, binding site 2, sequence conflict 2, chain 1, short sequence motif 1, modified residue 1, lipid moiety-binding region 1, disulfide bond 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35368-F1	67.95	0.28

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 (2): 125; 207

Post-translational modifications (2): 264, 365

Disulfide bonds (1): 118–195

Glycosylation sites (4): 10, 24, 29, 34

Mutagenesis-validated functional residues (1):

Position	Phenotype
368–380	abolishes targeting to the nuclear membrane of cardiac myocytes.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-390696	Adrenoceptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-162582	Signal Transduction
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-500792	GPCR ligand binding

MSigDB gene sets: 145 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, SEMENZA_HIF1_TARGETS, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_POSITIVE_REGULATION_OF_MUSCLE_HYPERTROPHY, GOBP_ADRENERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_MUSCLE_ADAPTATION, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_REGULATION_OF_MUSCLE_HYPERTROPHY

GO Biological Process (15): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), positive regulation of cardiac muscle hypertrophy (GO:0010613), regulation of vasoconstriction (GO:0019229), intracellular signal transduction (GO:0035556), positive regulation of MAPK cascade (GO:0043410), regulation of cardiac muscle contraction (GO:0055117), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), neuron-glial cell signaling (GO:0150099), regulation of muscle contraction (GO:0006937), signal transduction (GO:0007165), adrenergic receptor signaling pathway (GO:0071875)

GO Molecular Function (5): alpha1-adrenergic receptor activity (GO:0004937), protein heterodimerization activity (GO:0046982), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), caveola (GO:0005901), nuclear membrane (GO:0031965), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Amine ligand-binding receptors	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
signal transduction	2
cell communication	2
signaling	2
intracellular anatomical structure	2
adrenergic receptor signaling pathway	2
cellular anatomical structure	2
G protein-coupled receptor activity	1
adenylate cyclase activity	1
phospholipase C activator activity	1
regulation of biological quality	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of striated muscle contraction	1
regulation of heart contraction	1
cardiac muscle contraction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
cell-cell signaling	1
muscle contraction	1
regulation of muscle system process	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
adrenergic receptor activity	1
alpha-adrenergic receptor activity	1
protein dimerization activity	1
transmembrane signaling receptor activity	1
G protein-coupled amine receptor activity	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane raft	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRA1B	INPP1	P49441	766
ADRA1B	GNAQ	P50148	753
ADRA1B	TBXA2R	P21731	692
ADRA1B	ARRB1	P49407	683
ADRA1B	ARRB2	P32121	681
ADRA1B	SLC6A2	P23975	567
ADRA1B	AGT	P01019	547
ADRA1B	SLC6A3	Q01959	526
ADRA1B	SLC6A4	P31645	525
ADRA1B	EDN1	P05305	511
ADRA1B	HADHB	P55084	495
ADRA1B	ADRA2C	P18825	486
ADRA1B	TSHR	P16473	478
ADRA1B	C1QBP	Q07021	453
ADRA1B	JAK2	O60674	453

IntAct

24 interactions, top by confidence:

A	B	Type	Score
CXCR4	ADRA1B	psi-mi:“MI:2364”(proximity)	0.610
CXCR4	ADRA1A	psi-mi:“MI:0914”(association)	0.610
DRD4	ADRA1B	psi-mi:“MI:0915”(physical association)	0.470
DRD4	ADRA1B	psi-mi:“MI:2364”(proximity)	0.470
ACKR3	ADRA1B	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA2B	psi-mi:“MI:0914”(association)	0.420
ACKR3		psi-mi:“MI:2364”(proximity)	0.410
ADRA1B	ADRA1B	psi-mi:“MI:0915”(physical association)	0.400
ADRA1B	ADRA1A	psi-mi:“MI:0915”(physical association)	0.400
ADRA1B	ADRA1D	psi-mi:“MI:0915”(physical association)	0.400
ADRA1B	PPP1R9B	psi-mi:“MI:0915”(physical association)	0.400
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
ADRA1B		psi-mi:“MI:2364”(proximity)	0.270
FLNC	ADRA1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): ADRA1B (Affinity Capture-Western), ADRA1B (FRET), ADRA1B (FRET), ADRA1B (Affinity Capture-Western), ADRA1B (Affinity Capture-Western), ADRA1B (Proximity Label-MS), ADRA1B (Affinity Capture-Western), AP2M1 (Affinity Capture-Western), AP2M1 (Two-hybrid), ADRA1B (Affinity Capture-MS), ADRA1B (Proximity Label-MS), ADRA1B (Affinity Capture-MS)

ESM2 similar proteins: B2RPY5, B3DM66, O02824, O73810, O77680, P14416, P15823, P18130, P18841, P18901, P19020, P20288, P21728, P21918, P25115, P30728, P31389, P35348, P35367, P35368, P41596, P42288, P42290, P42291, P43140, P50130, P52702, P53452, P53453, P53454, P60026, P61168, P61169, P97717, P97718, Q16950, Q18775, Q19084, Q24563, Q2YDN1

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

23 interactions.

A	Effect	B	Mechanism
ADRA1B	“up-regulates activity”	GNAS	binding
ADRA1B	“up-regulates activity”	GNAL	binding
ADRA1B	“up-regulates activity”	GNAQ	binding
ADRA1B	“up-regulates activity”	GNA14	binding
(R)-noradrenaline	“up-regulates activity”	ADRA1B	“chemical activation”
terazosin	“down-regulates activity”	ADRA1B	“chemical inhibition”
PRKCA	“down-regulates activity”	ADRA1B	phosphorylation
(R)-adrenaline	“up-regulates activity”	ADRA1B	“chemical activation”
phentolamine	“down-regulates activity”	ADRA1B	“chemical inhibition”
methoxamine	“up-regulates activity”	ADRA1B	“chemical activation”
silodosin	“down-regulates activity”	ADRA1B	“chemical inhibition”
(S)-adrenaline	“up-regulates activity”	ADRA1B	“chemical activation”
oxymetazoline	“up-regulates activity”	ADRA1B	“chemical activation”
“(4S)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O5-[3-(4,4-diphenyl-1-piperidinyl)propyl] ester O3-methyl ester”	“down-regulates activity”	ADRA1B	“chemical inhibition”
N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine	“down-regulates activity”	ADRA1B	“chemical inhibition”
prazosin	“down-regulates activity”	ADRA1B	“chemical inhibition”
tamsulosin	“down-regulates activity”	ADRA1B	“chemical inhibition”
ADRA1B	“up-regulates activity”	GNA11	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

459 predictions. Top by Δscore:

Variant	Effect	Δscore
5:159917850:GCTTG:G	donor_gain	0.9900
5:159917855:G:C	donor_loss	0.9900
5:159917855:G:GG	donor_gain	0.9900
5:159917856:T:A	donor_loss	0.9900
5:159920508:C:CA	acceptor_gain	0.9900
5:159971874:TGCA:T	acceptor_loss	0.9900
5:159971875:GCA:G	acceptor_loss	0.9900
5:159971876:CA:C	acceptor_loss	0.9900
5:159971877:A:AG	acceptor_gain	0.9900
5:159971878:G:GA	acceptor_loss	0.9900
5:159971878:G:GC	acceptor_gain	0.9900
5:159917851:CTTG:C	donor_gain	0.9800
5:159943811:T:G	donor_gain	0.9800
5:159971877:AG:A	acceptor_gain	0.9800
5:159971878:GG:G	acceptor_gain	0.9800
5:159971878:GGCT:G	acceptor_gain	0.9800
5:159971878:GGCTC:G	acceptor_gain	0.9800
5:159917783:C:G	donor_gain	0.9700
5:159917853:TG:T	donor_gain	0.9600
5:159917854:GG:G	donor_gain	0.9600
5:159937293:G:GT	donor_gain	0.9600
5:159971872:A:AG	acceptor_gain	0.9600
5:159917852:TTG:T	donor_gain	0.9500
5:159971874:T:A	acceptor_gain	0.9500
5:159971878:GGC:G	acceptor_gain	0.9500
5:159971855:T:TA	acceptor_gain	0.9400
5:159971873:C:G	acceptor_gain	0.9300
5:159917857:AA:A	donor_loss	0.9000
5:159971872:ACT:A	acceptor_gain	0.9000
5:159971510:A:T	donor_gain	0.8800

AlphaMissense

3355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:159917308:A:C	S135R	1.000
5:159917310:C:A	S135R	1.000
5:159917310:C:G	S135R	1.000
5:159917333:G:C	R143P	1.000
5:159917539:T:C	F212L	1.000
5:159917541:C:A	F212L	1.000
5:159917541:C:G	F212L	1.000
5:159917812:T:C	F303L	1.000
5:159917814:C:A	F303L	1.000
5:159917814:C:G	F303L	1.000
5:159917089:G:C	G62R	0.999
5:159917094:C:A	N63K	0.999
5:159917094:C:G	N63K	0.999
5:159917163:C:A	N86K	0.999
5:159917163:C:G	N86K	0.999
5:159917165:T:C	L87P	0.999
5:159917176:G:C	D91H	0.999
5:159917177:A:C	D91A	0.999
5:159917177:A:G	D91G	0.999
5:159917177:A:T	D91V	0.999
5:159917178:C:A	D91E	0.999
5:159917178:C:G	D91E	0.999
5:159917188:A:C	S95R	0.999
5:159917190:C:A	S95R	0.999
5:159917190:C:G	S95R	0.999
5:159917238:G:C	W111C	0.999
5:159917238:G:T	W111C	0.999
5:159917257:T:A	C118S	0.999
5:159917258:G:A	C118Y	0.999
5:159917258:G:C	C118S	0.999

dbSNP variants (sampled 300 via entrez): RS1000012204 (5:159899438 C>G), RS1000027053 (5:159918994 T>C), RS1000032359 (5:159884718 T>C), RS1000044385 (5:159966025 T>C,G), RS1000072628 (5:159880514 G>A,C), RS1000104824 (5:159933969 A>G), RS1000114278 (5:159964846 G>A,T), RS1000144693 (5:159960030 G>C), RS1000144929 (5:159919299 G>T), RS1000178485 (5:159874955 G>A), RS1000179136 (5:159987305 C>A), RS1000182316 (5:159865441 G>A,T), RS1000198034 (5:159960234 G>A,C,T), RS1000203908 (5:159906028 T>G), RS1000214238 (5:159918059 G>C)

Disease associations

OMIM: gene MIM:104220 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003270_7	Psoriatic arthritis	1.000000e-24
GCST007094_96	Diastolic blood pressure	8.000000e-08
GCST007096_153	Pulse pressure	4.000000e-07
GCST007099_256	Systolic blood pressure	4.000000e-11
GCST008369_20	Plasma anti-thyroglobulin levels	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094251 (PROTEIN FAMILY), CHEMBL2095203 (PROTEIN FAMILY), CHEMBL2096676 (SELECTIVITY GROUP), CHEMBL232 (SINGLE PROTEIN), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

84 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 798,827 (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
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL134	CLONIDINE	4	97,993
CHEMBL1437	NOREPINEPHRINE	4	108,675
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1729	CISAPRIDE	4	14,365
CHEMBL1732	DIHYDROERGOTAMINE	4	12,897
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL24	ATENOLOL	4	48,715
CHEMBL279516	INDORAMIN	4	6,216
CHEMBL305660	EBASTINE	4	10,024
CHEMBL3187365	ASENAPINE	4	143
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL429	LABETALOL	4	23,037
CHEMBL434	ISOPROTERENOL	4	40,234
CHEMBL439849	VILAZODONE	4	1,555
CHEMBL49	BUSPIRONE	4	23,063
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL588	FENOLDOPAM	4	6,729
CHEMBL59	DOPAMINE	4	217,028
CHEMBL597	PHENTOLAMINE	4
CHEMBL611	TERAZOSIN	4
CHEMBL647	APRACLONIDINE	4
CHEMBL707	DOXAZOSIN	4
CHEMBL708	ZIPRASIDONE	4
CHEMBL709	ALFUZOSIN	4
CHEMBL715	OLANZAPINE	4
CHEMBL716	QUETIAPINE	4
CHEMBL770	TOLAZOLINE	4
CHEMBL836	TAMSULOSIN	4

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10515807	ADRA1B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (49 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]HEAT (BE2254)	Inverse agonist	10.2	pKd
MT-1207	Antagonist	10.07	pKi
(+)-cyclazosin	Inverse agonist	9.9	pKi
prazosin	Inverse agonist	9.9	pKi
compound 12 [PMID: 26238322]	Antagonist	9.8	pKi
tamsulosin	Inverse agonist	9.7	pKi
Rec 15/2615	Antagonist	9.5	pKi
(-)-adrenaline	Full agonist	9.4	pEC50
NAN 190	Antagonist	9.2	pKi
spiperone	Inverse agonist	9.2	pKi
(-)-noradrenaline	Full agonist	9.2	pEC50
[3H]prazosin	Inverse agonist	9.1	pKd
doxazosin	Antagonist	9.1	pKi
WB 4101	Antagonist	9.0	pKi
terazosin	Antagonist	8.7	pKi
alfuzosin	Antagonist	8.6	pKi
rho-TIA	Antagonist	8.4	pKi
A-119637	Antagonist	8.3	pKi
ketanserin	Antagonist	8.2	pKi
clozapine	Antagonist	8.2	pKi
muscarinic toxin β	Antagonist	8.0	pKi
mamba toxin CM-3	Antagonist	8.0	pKi
HEAT (BE2254)	Antagonist	8.0	pKd
A-123189	Antagonist	8.0	pKi
risperidone	Antagonist	8.0	pKi

Binding affinities (BindingDB)

51 measured of 79 human assays (86 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[(2R)-2-{[2-(2-ethoxyphenoxy)ethyl]amino}propyl]-2-methoxybenzenesulfonamide	KI	0.029 nM
NSC_104911	KI	0.1 nM
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
NSC_60147	KI	0.19 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
Rec 27/0074	KI	0.89 nM
Rec 27/0224	KI	1.05 nM
NSC_16041629	KI	1.7 nM
6,7-dimethoxy-2-[4-(tetrahydrofuran-2-ylcarbonyl)piperazin-1-yl]quinazolin-4-amine	KI	1.82 nM
Permax	KI	1.91 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	KI	2.94 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
CHEMBL1907861	KI	3 nM
Terguride	KI	3.47 nM
CAS_16041092	KI	3.6 nM
S18616	KI	3.98 nM
NSC_16041630	KI	5.3 nM
CHEMBL78986	KI	6.7 nM
CAS_16041091	KI	11 nM
NSC_16041263	KI	11 nM
Bromocriptine+ (GTP+)	KI	12.9 nM
NSC_16041628	KI	14 nM
CHEMBL1907669	KI	17 nM
NSC_54746	KI	19.9 nM
NSC_16041264	KI	22 nM
CAS_172307	KI	25.1 nM
NSC_16041265	KI	33 nM
Fluorocarazolol,(S)	KI	34 nM
LY 246708	KI	50.1 nM
CAS_16041449	KI	51 nM
NSC_16041451	KI	101 nM
CAS_16041090	KI	110 nM
CAS_16040907	KI	155 nM
CAS_105182-45-4	KI	158 nM
(R)-5-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole	KI	200 nM
S32504	KI	257 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one	KI	288 nM
NSC_4850	KI	447 nM
CAS_85760-74-3	IC50	462 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
Pramipexole	KI	692 nM
(R)-4-Methyl-1-(2-(1-(naphthalene-1-sulfonyl)-pyrrolidin-2-yl)-ethyl)-piperidine(10)	KI	1000 nM
(R)-4-Methyl-1-(2-(1-toluene-3-sulfonyl)-pyrrolidin-2-yl)-ethyl)-piperidine (Oxalate salt)	KI	1000 nM
(R)-1-(2-(1-(3,4-Dichloro-benzene sulfonyl)-pyrrolidin-2-yl)-ethyl)-4-methyl piperidine	KI	1580 nM
(R)-4-Methyl-1-(2-(1-(naphthalene-1-sulfonyl)-piperidin-2-yl)-ethyl)-piperidine(5)	KI	1580 nM
2-(3-(5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-8-yl)-4-hydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	IC50	1630 nM
B-HT 920	KI	1700 nM
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
MDL-11939	KI	3420 nM
(6,7-Dihydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-dimethyl-ammonium	KI	3800 nM
SB-258719	KI	5010 nM

ChEMBL bioactivities

2237 potent at pChembl≥5 of 2273 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.57	Ki	0.027	nM	PRAZOSIN
10.42	Ki	0.038	nM	CHEMBL25554
10.40	Ki	0.03981	nM	CHEMBL42472
10.40	Kd	0.03981	nM	TAMSULOSIN
10.27	Ki	0.054	nM	PRAZOSIN
10.20	Ki	0.063	nM	PRAZOSIN
10.15	Ki	0.07079	nM	CHEMBL342062
10.10	Ki	0.08	nM	ABANOQUIL
10.07	Ki	0.086	nM	CHEMBL5618291
10.00	Ki	0.1	nM	CHEMBL3582270
10.00	Ki	0.1	nM	CHEMBL196961
10.00	Ki	0.1	nM	CHEMBL198462
10.00	Ki	0.1	nM	CHEMBL196958
9.96	Ki	0.11	nM	ABANOQUIL
9.96	Ki	0.1096	nM	CHEMBL27013
9.89	EC50	0.13	nM	TAMSULOSIN
9.89	Ki	0.1288	nM	CHEMBL4126860
9.87	Ki	0.1349	nM	CHEMBL342062
9.87	Ki	0.1349	nM	(+)-CYCLAZOSIN
9.87	Ki	0.1349	nM	CYCLAZOSIN
9.82	Ki	0.1514	nM	CHEMBL4129291
9.82	IC50	0.15	nM	CHEMBL5618291
9.80	Ki	0.1585	nM	CHEMBL198860
9.80	Kd	0.1585	nM	TAMSULOSIN
9.78	Ki	0.166	nM	CHEMBL341665
9.77	IC50	0.17	nM	PRAZOSIN
9.72	Ki	0.1905	nM	CHEMBL4128084
9.70	IC50	0.2	nM	PRAZOSIN
9.70	Ki	0.2	nM	CHEMBL200315
9.70	Ki	0.2	nM	CHEMBL197338
9.70	Ki	0.2	nM	CHEMBL371094
9.70	Ki	0.1995	nM	CYCLAZOSIN
9.68	Ki	0.21	nM	PRAZOSIN
9.62	Ki	0.2399	nM	CHEMBL242724
9.60	Ki	0.2512	nM	CHEMBL200366
9.60	Ki	0.2512	nM	CHEMBL199080
9.60	Ki	0.2512	nM	PRAZOSIN
9.59	IC50	0.26	nM	PRAZOSIN
9.55	Ki	0.2818	nM	CHEMBL4161165
9.55	Ki	0.28	nM	PRAZOSIN
9.52	Ki	0.302	nM	CHEMBL4127483
9.51	Ki	0.309	nM	CYCLAZOSIN
9.51	Ki	0.309	nM	CHEMBL2261605
9.51	Ki	0.309	nM	CHEMBL178673
9.51	Ki	0.309	nM	CHEMBL388884
9.49	Ki	0.3236	nM	CYCLAZOSIN
9.49	Ki	0.32	nM	PRAZOSIN
9.48	Ki	0.33	nM	CHEMBL61483
9.42	Ki	0.3802	nM	CHEMBL4125981
9.42	Kd	0.3802	nM	PRAZOSIN

PubChem BioAssay actives

2169 with measured affinity, of 3800 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
2-(2,6-dimethoxyphenoxy)-N-[[(2S,4R)-4-phenyl-3,4-dihydro-2H-chromen-2-yl]methyl]ethanamine	37358: Affinity constant on CHO cells expressing Human recombinant Alpha-1B adrenergic receptor	ki	<0.0001	uM
Tamsulosin	36126: Activity against Alpha-1 adrenergic receptor subtypes of human prostate tissue	kd	<0.0001	uM
Prazosin	2093571: Binding affinity to recombinant human alpha-1B-Adr expressed in HEK cells assessed as inhibition constant	ki	<0.0001	uM
N-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine	1581729: Displacement of [3H]prazosin from human recombinant adrenergic alpha-1B receptor expressed in CHO cell membranes incubated for 60 mins	ki	<0.0001	uM
3-[4-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazine-1-carbonyl]triazol-1-yl]-7-(diethylamino)chromen-2-one	1229076: Displacement of [3H]-Prazosin from human alpha-1B adrenergic receptor transfected in CHO cell membranes after 2 hrs by microplate scintillation counting analysis	ki	0.0001	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0001	uM
N-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl]-N-methylfuran-2-carboxamide	37487: Binding affinity at human cloned Alpha-1B adrenergic receptor in chinese hamster ovary cells by [3H]prazosin displacement.	ki	0.0001	uM
[(4aS,8aR)-4-[4-(dipropylamino)-6,7-dimethoxyquinazolin-2-yl]-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0001	uM
3-[4-[4-(benzotriazol-1-yl)butyl]piperazin-1-yl]-1,2-benzothiazole;hydrochloride	2128214: Displacement of [3H]prazosin from recombinant human alpha 1B adrenoceptor extracted from CHO cell membrane incubated for 60 mins by radioligand binding assay	ic50	0.0001	uM
2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-6,7-dimethoxyquinolin-4-amine	37183: Binding affinity against Alpha-1B adrenergic receptor from hamster clones.	ki	0.0001	uM
4-[2-[4-(5-chloro-2-methoxyphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0001	uM
4-[2-[4-(2-methoxy-5-phenylphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0001	uM
11-methyl-4-[2-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]ethyl]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0001	uM
[(4aS,8aR)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0001	uM
N-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl]-3-[(dimethylamino)methyl]-N-methylbenzamide	37487: Binding affinity at human cloned Alpha-1B adrenergic receptor in chinese hamster ovary cells by [3H]prazosin displacement.	ki	0.0002	uM
2-[2-[(3-chlorophenyl)methoxy]phenoxy]-N-[2-(2,6-dimethoxyphenoxy)ethyl]ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0002	uM
4-[2-[4-[2-(2,2-dimethylpropoxy)phenyl]piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0002	uM
4-[2-[4-(2,3-dihydro-1-benzofuran-7-yl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0002	uM
4-[2-[4-(4,5-dichloro-2-methoxyphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0002	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-thiophen-2-ylmethanone	294002: Displacement of [3H]prazosin from human adrenergic alpha-1b receptor expressed in CHO cells	ki	0.0002	uM
1-[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-2-(2-methoxy-6-propan-2-ylphenoxy)ethanone	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0002	uM
benzyl (4aS,8aR)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxaline-1-carboxylate	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0002	uM
3-[2-[(3aR,9bR)-6-methoxy-1,3,3a,4,5,9b-hexahydrobenzo[e]isoindol-2-yl]ethyl]-7-phenyl-1H-thieno[3,2-d]pyrimidine-2,4-dione	37068: Binding affinity to hamster alpha-1B adrenergic receptor	ki	0.0003	uM
1-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-2-(dithiolan-3-yl)ethanone	239824: Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]prazosin to label cloned human alpha 1b expressed in CHO cells	ki	0.0003	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(4-methylphenyl)methoxy]phenoxy]ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0003	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(3-methylphenyl)methoxy]phenoxy]ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0003	uM
N-[(3S)-1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl]furan-2-carboxamide	1507225: Displacement of [3H]prazosin from human alpha1B adrenoceptor expressed in CHO cell membranes after 30 mins	ki	0.0003	uM
[(4aR,8aS)-4-[4-(dipropylamino)-6,7-dimethoxyquinazolin-2-yl]-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0003	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(5-bromofuran-2-yl)methanone	294002: Displacement of [3H]prazosin from human adrenergic alpha-1b receptor expressed in CHO cells	ki	0.0003	uM
N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-5-methyl-2-methylsulfanylaniline	37346: Agonist potency at Alpha-1B adrenergic receptor expressed in rat-1 fibroblasts	ec50	0.0004	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(4-nitrophenyl)methoxy]phenoxy]ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0004	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(4-methoxyphenyl)methoxy]phenoxy]ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0004	uM
methyl 2-(4,5-dihydro-1H-imidazol-2-ylmethylamino)benzoate	32970: Potency against cloned human alpha 1B adrenoceptor expressed in rat-1 fibroblasts.	ec50	0.0004	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(2,3-dihydro-1,4-benzodioxin-3-yl)methanone	422825: Displacement of [3H]prazosin from human Alpha-1B adrenoceptor expressed in CHO cells	ki	0.0004	uM
benzyl (4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxaline-1-carboxylate	1497048: Displacement of [3H]prazosin from human alpha1B adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0004	uM
4-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0004	uM
1-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-2-(2-methoxy-6-propan-2-ylphenoxy)ethanone	35175: The binding affinity towards Alpha-1B adrenergic receptor in the COS cell line.	ki	0.0004	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-(2-phenylmethoxyphenoxy)ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0005	uM
5-chloro-N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-2-methylsulfanylaniline	37346: Agonist potency at Alpha-1B adrenergic receptor expressed in rat-1 fibroblasts	ec50	0.0005	uM
[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(dithiolan-3-yl)methanone	239824: Equilibrium dissociation constant was evaluated by radio-receptor binding assays using [3H]prazosin to label cloned human alpha 1b expressed in CHO cells	ki	0.0005	uM
2-[[(3S)-1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl]amino]naphthalene-1,4-dione	1507225: Displacement of [3H]prazosin from human alpha1B adrenoceptor expressed in CHO cell membranes after 30 mins	ki	0.0005	uM
2-[4-(furan-2-yl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine	35175: The binding affinity towards Alpha-1B adrenergic receptor in the COS cell line.	ki	0.0005	uM
11-methyl-4-[2-[4-(2-phenoxyphenyl)piperazin-1-yl]ethyl]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0005	uM
4-[2-[4-(1-benzothiophen-7-yl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0005	uM
4-[2-[4-(4-chloro-2-methoxyphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0005	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-phenylmethanone	294002: Displacement of [3H]prazosin from human adrenergic alpha-1b receptor expressed in CHO cells	ki	0.0005	uM
N-[2-(2,6-dimethoxyphenyl)sulfanylethyl]-2-(2-phenylmethoxyphenoxy)ethanamine	515614: Displacement of [3H]prazosin from human adrenergic Alpha-1B expressed in CHO cells	ki	0.0005	uM
Terazosin	1194511: Antagonist activity at alpha-1B adrenergic receptor (unknown origin) incubated for 30 mins prior to agonist addition measured after 5 hrs by CCF4-AM staining-based cellular assay	ec50	0.0005	uM
4-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamino]-2-methyl-5-(2-methylpropanoyl)-6-phenylpyridazin-3-one	218799: Binding affinity towards human cloned alpha-1B-adrenoceptor using [3H]prazosin as radioligand	ki	0.0006	uM
2-[2-[(2-chlorophenyl)methoxy]phenoxy]-N-[2-(2,6-dimethoxyphenoxy)ethyl]ethanamine	257358: Displacement of [3H]prazosin from cloned human ADRA1B expressed in CHO cells	ki	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Calcium	affects binding, decreases reaction, increases abundance, increases activity	3
Phenylephrine	decreases reaction, increases phosphorylation, increases abundance, increases activity, affects response to substance (+1 more)	3
Prazosin	affects binding, decreases reaction	3
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Dexamethasone	increases expression, affects cotreatment	2
Epinephrine	increases activity, affects binding, decreases reaction, increases abundance	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression, affects cotreatment	1
xylometazoline	affects binding, decreases reaction	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
ferrous chloride	decreases expression	1
Terazosin	affects binding	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
alfuzosin	affects binding	1
2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone	affects binding	1
BMY 7378	affects binding	1
abanoquil	affects binding	1
sarpogrelate	affects binding, decreases reaction	1
fipronil	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
1-(2-(3-methoxyphenyl)ethyl)phenoxy-3-(dimethylamino)-2-propanol	affects binding, decreases reaction	1
bardoxolone methyl	decreases activity	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Carvedilol	increases abundance, increases activity, affects cotreatment, increases phosphorylation, affects binding (+2 more)	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

728 unique, capped per target: 603 binding, 115 functional, 10 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110026	Binding	Binding affinity to human alpha1 adrenergic receptor by radioligand displacement assay	Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia. — Bioorg Med Chem Lett
CHEMBL3635163	Functional	Agonist activity at adrenergic a1 receptor (unknown origin) expressed in CHO cells assessed as calcium mobilization at 3 uM	Discovery of dihydroquinazolinone derivatives as potent, selective, and CNS-penetrant M(1) and M(4) muscarinic acetylcholine receptors agonists. — Bioorg Med Chem Lett
CHEMBL4729785	ADMET	Binding affinity to alpha1 adrenergic receptor (unknown origin)	Synthesis and pharmacological evaluation of piperidine (piperazine)-amide substituted derivatives as multi-target antipsychotics. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 4 spontaneously immortalized cell line, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9110	L-alpha-1b L-cells	Spontaneously immortalized cell line	Male
CVCL_D7JQ	Ubigene A-549 ADRA1B KO	Cancer cell line	Male
CVCL_D9X8	Ubigene HeLa ADRA1B KO	Cancer cell line	Female
CVCL_H388	CHO-K1/ADRA1B	Spontaneously immortalized cell line	Female
CVCL_KB31	GeneBLAzer ADRA1B-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KW25	PathHunter CHO-K1 ADRA1B beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_YK28	U2OS ADRA1B DAG-Nomad	Cancer cell line	Female
CVCL_YK29	U2OS ADRA1B HiTSeeker	Cancer cell line	Female

Clinical trials (associated diseases)

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