BDKRB1

Summary

BDKRB1 (bradykinin receptor B1, HGNC:1029) is a protein-coding gene on chromosome 14q32.2, encoding B1 bradykinin receptor (P46663). This is a receptor for bradykinin.

Bradykinin, a 9 aa peptide, is generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The protein encoded by this gene belongs to the G-protein coupled receptor 1 family. Two types of G-protein coupled receptors have been found which bind bradykinin and mediate responses to these pathophysiologic conditions. The protein encoded by this gene is one of these receptors and is synthesized de novo following tissue injury. Receptor binding leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses.

Source: NCBI Gene 623 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1029
Approved symbol	BDKRB1
Name	bradykinin receptor B1
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	BKR1, B1BKR, bradyb1
Ensembl gene	ENSG00000100739
Ensembl biotype	protein_coding
OMIM	600337
Entrez	623

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000216629, ENST00000553356, ENST00000557122, ENST00000611804, ENST00000863471, ENST00000863472

RefSeq mRNA: 2 — MANE Select: NM_000710 NM_000710, NM_001386007

CCDS: CCDS9943

Canonical transcript exons

ENST00000216629 — 3 exons

Exon	Start	End
ENSE00000660133	96263673	96264763
ENSE00001513977	96256210	96256300
ENSE00003561350	96262652	96262770

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 96.14.

FANTOM5 (CAGE): breadth broad, TPM avg 7.4346 / max 402.5137, expressed in 539 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141335	6.8714	524
141329	4.9703	898
207358	0.2167	128
141334	0.1006	47
141332	0.0991	43
141331	0.0746	42
141333	0.0721	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.02	gold quality
gall bladder	UBERON:0002110	83.58	gold quality
stromal cell of endometrium	CL:0002255	81.79	gold quality
mucosa of transverse colon	UBERON:0004991	81.37	gold quality
lower esophagus mucosa	UBERON:0035834	81.34	gold quality
esophagus mucosa	UBERON:0002469	80.98	gold quality
ectocervix	UBERON:0012249	77.11	gold quality
endocervix	UBERON:0000458	74.96	gold quality
vagina	UBERON:0000996	74.27	gold quality
omental fat pad	UBERON:0010414	73.87	gold quality
esophagus	UBERON:0001043	73.22	gold quality
body of pancreas	UBERON:0001150	72.53	gold quality
vermiform appendix	UBERON:0001154	71.69	gold quality
uterine cervix	UBERON:0000002	71.45	gold quality
pancreas	UBERON:0001264	70.80	gold quality
metanephros cortex	UBERON:0010533	70.50	gold quality
transverse colon	UBERON:0001157	69.65	gold quality
rectum	UBERON:0001052	68.75	gold quality
left uterine tube	UBERON:0001303	68.39	gold quality
islet of Langerhans	UBERON:0000006	68.21	gold quality
smooth muscle tissue	UBERON:0001135	68.10	gold quality
skin of abdomen	UBERON:0001416	67.85	gold quality
colon	UBERON:0001155	67.21	gold quality
zone of skin	UBERON:0000014	66.99	gold quality
adult mammalian kidney	UBERON:0000082	66.56	gold quality
skin of leg	UBERON:0001511	66.52	gold quality
intestine	UBERON:0000160	66.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	65.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	2185.08
E-ANND-3	yes	7.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, ETV4, GATA1, GTF2B, JUN, NFKB1, POU1F1, POU2F1, RELA, SP1, TBP, TP53, YY1

Literature-anchored findings (GeneRIF, showing 40)

• B1 and B2 receptor expression was enhanced in tumor cells and tissue adjacent to gastric cancer compared with gastric ulcers. (PMID:11710536)
• Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor (PMID:11880373)
• Bradykinin B1 receptors are upregulated by inflammatory stimuli in bronchial epithelial cells. (PMID:12063092)
• the C-terminal domain participates intimately in the efficacy of B1R and B2R G(q/11) coupling by contributing both positive and negative regulatory epitopes. (PMID:12130679)
• Allergic rhinitis subjects displayed significantly higher expression of B1 receptor mRNA than did the normal subjects. (PMID:12165532)
• B1R exists in caveolae-related lipid rafts (CLRs) in HEK293 cells apparently by default, as a result of their random distribution in the plasma membrane and not by being targeted to the CLR fraction. (PMID:12450400)
• B1 and B2 bradykinin receptors form a complex with enhanced signaling capacity (PMID:15033977)
• Bradykinin B(1) receptor homooligomerization is required for expression of receptors on the cell surface and subsequent constitutive receptor signaling. (PMID:15492119)
• kinin B(1) receptors participate in painful and inflammatory disorders–REVIEW (PMID:15520046)
• slow internalization of B(1)KB(2) was also accompanied by a lack of agonist-induced phosphorylation, that in contrast was observed for B(1)YB(2) and B(1)CB(2), suggesting that putative helix 8 is either directly or indirectly involved (PMID:15634338)
• the two bradykinin receptors may play a role in blood pressure regulation (PMID:15643125)
• The B1 kinin receptor does not have a major vasomotor or fibrinolytic role in patients with heart failure (PMID:15681300)
• Use of the highly sensitive DNase I in vivo footprinting approach to delineate more precisely the functional domains of the BDKRB1 gene promoter in human smooth muscle cells is reported. (PMID:15705059)
• bradykinin receptors in imflammatory bowel disease may reflect intestinal inflammation (PMID:15805101)
• A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed using structure-activity relationship studies. (PMID:15837330)
• BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure. (PMID:15840906)
• Kinin B1 receptor expression on multiple sclerosis mononuclear cells (PMID:15883268)
• Increased level of bradykinin receptor B1 in adenoma suggests that kinins may play a role in abnormal cellular transformation. (PMID:16644486)
• kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell surface. (PMID:17110500)
• B1 bradykinin binding pocket for agonists and antagonists is similar (PMID:17128974)
• The novel finding that kinin receptors are constitutively expressed in immature hMo-DC suggests that these receptors may be expressed in the absence of proinflammatory stimuli. (PMID:17327486)
• Kinin B1 and B2 receptors synergistically potentiate IL-1- and TNFalpha-induced PG biosynthesis in osteoblasts by a mechanism involving increased levels of COX-2, resulting in increased RANKL (PMID:17328065)
• The study showed 7-fold higher transcriptional activity of bradykinin 1 receptor in patients with cardiac syndrome X than in control patients. (PMID:17852785)
• unveils a proinflammatory pathway centered on kinin B1 receptor activation of CXCL5 leading to leukocyte trafficking (PMID:17878384)
• Corticosteroids may have a beneficial anti-inflammatory effect in asthma by down-regulating B(1) receptor expression on neutrophils, thereby decreasing the migration of these inflammatory cells into the airways (PMID:18039523)
• We suggest that increased expression of B1 receptor in the human airway following a URI could increase the risk of an exacerbation of asthma by contributing to increased inflammation in the airway. (PMID:18039525)
• Carboxypeptidase M and kinin B1 receptors interact to facilitate efficient b1 signaling from B2 agonists (PMID:18187413)
• These data show that IL-1beta and TNF-alpha upregulate B1 and B2 receptor expression by mechanisms involving activation of both NF-kappaB and MAP kinase pathways, but that signal transduction pathways are different for IL-1beta and TNF-alpha. (PMID:18467203)
• The kallikrein-kinin system may be one of the more important players in angiogenesis associated with prostate and breast tumours. (PMID:18577888)
• The role of B1 receptors on renal fibrosis and the use of a nonpeptide B1R antagonist on the progression of obstructive kidney disease is reported. (PMID:18809736)
• RT-PCR demonstrates the presence of mRNAs for brradykinin B1 receptors in a human embryo kidney cell line. (PMID:18938142)
• Eosinophils in asthmatic patients expressed significantly greater kinin B(1)R and B(2)R mRNA and proteins (PMID:19038786)
• The ratio of bradykinin subtype 1 receptor (B1R) to bradykinin subtype 2 receptor (B2R)is markedly higher in patients with acute coronary syndrome versus the age-matched healthy control group. (PMID:19120546)
• B(1)R-epidermal growth factor receptor crosstalk may be a key interaction that maintains tumor growth (PMID:19184415)
• Epithelial cells, submucosal glands, fibroblast, vascular smooth muscle, vascular endothelial cells, and macrophages showed immunoreactivity for both B1 and B2 receptors. (PMID:19404481)
• BK-1 receptor plays a pivotal role in inflammatory disorders in neutrophils. (PMID:19641039)
• Laminar shear stress is a major determinant of functional B1R expression in endothelium. (PMID:19661485)
• B1R and B2R activation, which may result from an increase in BK synthesis, is involved in high glucose-induced stimulation of glutamate uptake, COX-2 expression, and NF-kB activation, in retinal pigment epithelium cells. (PMID:19725054)
• both B1 receptor and gC1q receptor are involved in the vascular leakage induced by hereditary and acquired angioedema plasma. (PMID:19796797)
• human chondrosarcoma tissues had significantly higher expression of the B1 and B2 receptors comparing to normal cartilage (PMID:19885862)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bdkrb1	ENSDARG00000020744
mus_musculus	Bdkrb1	ENSMUSG00000041347
rattus_norvegicus	Bdkrb1	ENSRNOG00000004488
caenorhabditis_elegans		WBGENE00015559

Paralogs (7): APLNR (ENSG00000134817), AGTR1 (ENSG00000144891), GPR15 (ENSG00000154165), BDKRB2 (ENSG00000168398), GPR25 (ENSG00000170128), RXFP4 (ENSG00000173080), AGTR2 (ENSG00000180772)

Protein

Protein identifiers

B1 bradykinin receptor — P46663 (reviewed: P46663)

All UniProt accessions (2): P46663, G3V4Y2

UniProt curated annotations — full annotation on UniProt →

Function. This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.

Subcellular location. Cell membrane.

Similarity. Belongs to the G-protein coupled receptor 1 family. Bradykinin receptor subfamily. BDKRB1 sub-subfamily.

RefSeq proteins (2): NP_000701, NP_001372936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000496	Brdyknn_rcpt	Family
IPR001186	Brdyknn_1_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (46 total): helix 13, topological domain 8, transmembrane region 7, sequence conflict 4, turn 4, glycosylation site 3, sequence variant 2, strand 2, chain 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7EIB	ELECTRON MICROSCOPY	3
9LFA	ELECTRON MICROSCOPY	3.5
9LFC	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46663-F1	85.25	0.63

Functional residue map

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

Post-translational modifications (1): 330

Disulfide bonds (1): 110–189

Glycosylation sites (3): 14, 22, 185

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 156 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL, AMIT_EGF_RESPONSE_480_MCF10A, GOBP_LEUKOCYTE_MIGRATION, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MODULE_289, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT

GO Biological Process (11): positive regulation of leukocyte migration (GO:0002687), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), response to mechanical stimulus (GO:0009612), cell migration (GO:0016477), negative regulation of cell growth (GO:0030308), response to lipopolysaccharide (GO:0032496), negative regulation of blood pressure (GO:0045776), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), signal transduction (GO:0007165)

GO Molecular Function (4): bradykinin receptor activity (GO:0004947), peptide binding (GO:0042277), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
positive regulation of immune system process	1
regulation of leukocyte migration	1
positive regulation of cell migration	1
leukocyte migration	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological quality	1
response to external stimulus	1
response to abiotic stimulus	1
cell motility	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
regulation of blood pressure	1
release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled peptide receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BDKRB1	KNG1	P01042	999
BDKRB1	ACE	P12821	875
BDKRB1	VRK2	Q86Y07	875
BDKRB1	VRK1	Q99986	852
BDKRB1	KLK4	Q9Y5K2	832
BDKRB1	CPM	P14384	786
BDKRB1	AGT	P01019	748
BDKRB1	GNAQ	P50148	739
BDKRB1	TRPA1	O75762	705
BDKRB1	CHRM3	P20309	693
BDKRB1	AGTRAP	Q6RW13	648
BDKRB1	KLKB1	P03952	644
BDKRB1	TRPV1	Q8NER1	570
BDKRB1	KLK1	P06870	568
BDKRB1	TRPM8	Q7Z2W7	564

IntAct

40 interactions, top by confidence:

A	B	Type	Score
BDKRB1	KNG1	psi-mi:“MI:0915”(physical association)	0.400
BDKRB1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	BDKRB1	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	BDKRB1	psi-mi:“MI:0915”(physical association)	0.400
BDKRB1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
C1orf43	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
DNAJB1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
RETREG1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
GABBR1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
GRIN1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
HHATL	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
HTT	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
HILPDA	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
INSIG1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
CERS1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
LRRC4C	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
LAPTM4B	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
MDC1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
MBOAT7	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
NAGPA	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
NDFIP1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
NF2	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
NAP1L4	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
OAZ2	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
RAE1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
RTN4	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
SLC25A28	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (32): C1orf43 (Two-hybrid), DNAJB1 (Two-hybrid), FAM134B (Two-hybrid), GABBR1 (Two-hybrid), GRIN1 (Two-hybrid), HHATL (Two-hybrid), HTT (Two-hybrid), HILPDA (Two-hybrid), INSIG1 (Two-hybrid), CERS1 (Two-hybrid), LRRC4C (Two-hybrid), LAPTM4B (Two-hybrid), MDC1 (Two-hybrid), MBOAT7 (Two-hybrid), NAGPA (Two-hybrid)

ESM2 similar proteins: A0T2N3, F7EQ49, O08878, O70526, O88410, O88855, P30411, P46093, P46663, P48146, P49220, P49681, P49682, P49684, P50132, P51680, P51686, P56484, P79960, P97583, Q15722, Q1JQB3, Q1WLP9, Q28642, Q2TAD5, Q3BCU0, Q3T181, Q4KLH9, Q4VA82, Q56UD9, Q5KSK8, Q5MD61, Q61125, Q7SZP9, Q867B2, Q8BMP4, Q8BUD0, Q8HZN9, Q8HZP1, Q8HZP2

Diamond homologs: A0T2N3, E9QJ73, O00155, O00590, O08858, O18982, O35210, O42179, O55197, O77590, O88680, O89039, O97571, O97663, O97666, P0C5I1, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30938, P32248, P32303, P33396, P34976, P35343, P35346, P35351, P35373, P35374, P35407, P35414

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
bradykinin	up-regulates	BDKRB1	“chemical activation”
BDKRB1	“up-regulates activity”	GNAS	binding
BDKRB1	“up-regulates activity”	GNAL	binding
BDKRB1	“up-regulates activity”	GNAI1	binding
BDKRB1	“up-regulates activity”	GNAI3	binding
BDKRB1	“up-regulates activity”	GNAO1	binding
BDKRB1	“up-regulates activity”	GNAQ	binding
BDKRB1	“up-regulates activity”	GNA14	binding
BDKRB1	“up-regulates activity”	GNA15	binding
bradykinin	“up-regulates activity”	BDKRB1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

218 predictions. Top by Δscore:

Variant	Effect	Δscore
14:96256296:CCTGA:C	donor_gain	0.9900
14:96256297:CTGA:C	donor_gain	0.9900
14:96256298:TGA:T	donor_gain	0.9900
14:96256299:GA:G	donor_gain	0.9900
14:96256299:GAG:G	donor_gain	0.9900
14:96256301:G:GG	donor_gain	0.9900
14:96256300:AG:A	donor_loss	0.9800
14:96256301:GTAA:G	donor_loss	0.9800
14:96256305:G:GG	donor_gain	0.9800
14:96256303:AA:A	donor_loss	0.9700
14:96263667:TTTCA:T	acceptor_loss	0.9700
14:96263668:TTCAG:T	acceptor_loss	0.9700
14:96263669:TCAG:T	acceptor_loss	0.9700
14:96263670:CA:C	acceptor_loss	0.9700
14:96263671:A:AC	acceptor_loss	0.9700
14:96263671:A:AG	acceptor_gain	0.9700
14:96263671:A:T	acceptor_loss	0.9700
14:96263672:G:C	acceptor_loss	0.9700
14:96263672:G:GG	acceptor_gain	0.9700
14:96263666:A:AG	acceptor_gain	0.9500
14:96256304:A:AG	donor_gain	0.9400
14:96256304:A:AT	donor_loss	0.9300
14:96262651:G:GC	acceptor_gain	0.9300
14:96263344:A:T	donor_gain	0.9200
14:96263672:GGTC:G	acceptor_gain	0.9100
14:96263672:GGTCA:G	acceptor_gain	0.9100
14:96256309:A:G	donor_gain	0.8900
14:96262651:GGGTC:G	acceptor_gain	0.8900
14:96263672:GGT:G	acceptor_gain	0.8800
14:96262650:AG:A	acceptor_gain	0.8700

AlphaMissense

2299 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:96263991:G:C	W103C	0.995
14:96263991:G:T	W103C	0.995
14:96264457:T:C	F259L	0.994
14:96264459:C:A	F259L	0.994
14:96264459:C:G	F259L	0.994
14:96264187:A:C	S169R	0.990
14:96264189:C:A	S169R	0.990
14:96264189:C:G	S169R	0.990
14:96264052:A:C	S124R	0.989
14:96264054:C:A	S124R	0.989
14:96264054:C:G	S124R	0.989
14:96264076:A:C	S132R	0.989
14:96264078:C:A	S132R	0.989
14:96264078:C:G	S132R	0.989
14:96264010:T:A	C110S	0.988
14:96264011:G:C	C110S	0.988
14:96264595:A:C	S305R	0.988
14:96264597:C:A	S305R	0.988
14:96264597:C:G	S305R	0.988
14:96264247:T:A	C189S	0.987
14:96264248:G:C	C189S	0.987
14:96264249:C:G	C189W	0.987
14:96264313:T:C	F211L	0.987
14:96264315:C:A	F211L	0.987
14:96264315:C:G	F211L	0.987
14:96263930:A:C	D83A	0.986
14:96264584:C:A	A301D	0.986
14:96263781:G:C	W33C	0.985
14:96263781:G:T	W33C	0.985
14:96263989:T:A	W103R	0.985

dbSNP variants (sampled 300 via entrez): RS1000091722 (14:96263797 G>A), RS1000345993 (14:96259870 C>T), RS1000652713 (14:96259309 A>G), RS1001439191 (14:96258650 A>T), RS1001752758 (14:96258478 G>T), RS1001891789 (14:96258410 A>G), RS1002182451 (14:96263099 G>A), RS1002354135 (14:96256919 G>A), RS1002388499 (14:96259932 C>T), RS1002439482 (14:96259715 T>C), RS1003134841 (14:96261567 A>G), RS1003185329 (14:96261797 C>T), RS1003387410 (14:96255506 C>T), RS1003446046 (14:96261116 A>G), RS1004206992 (14:96256982 G>A,T)

Disease associations

OMIM: gene MIM:600337 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_198	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010483	gentisic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4308 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 132,576 (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
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL374478	RIFAMPIN	4	93,834
CHEMBL1254771	SAFOTIBANT	2	90
CHEMBL232943	MK0686	2	25

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12050217	Efficacy	3	perindopril	Coronary Artery Disease

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12050217	BDKRB1	3	5.50	1	perindopril

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Bradykinin receptors

Most potent curated ligand interactions (36 total), top 25:

Ligand	Action	Affinity	Parameter
compound 11 [PMID: 12812482]	Antagonist	10.5	pKi
B-9858	Antagonist	10.4	pKi
B-9958	Antagonist	10.29	pKi
B-10356	Antagonist	10.2	pKi
NPC 18565	Antagonist	10.2	pKi
[125I]Hpp-desArg10HOE140	Antagonist	10.0	pKd
[des-Arg10]kallidin	Full agonist	10.0	pKi
NG29	Full agonist	9.5	pIC50
D-Lys0-[des-Arg10]kallidin	Full agonist	9.5	pKi
[3H]Lys-[des-Arg9]BK	Full agonist	9.4	pKd
compound 12 [PMID: 12723943]	Antagonist	9.2	pKi
SSR240612	Antagonist	9.2	pKi
[Leu9,des-Arg10]kallidin	Antagonist	8.9	pIC50
kallidin	Full agonist	8.9	pKi
R-954	Antagonist	8.6	pA2
R-715	Antagonist	8.5	pA2
chroman 28	Antagonist	8.5	pIC50
[des-Arg10]icatibant	Antagonist	8.4	pKi
PS020990	Antagonist	8.2	pKi
NVP-SAA164	Antagonist	8.1	pKi
B-9430	Antagonist	7.9	pKi
[D-Lys1,des-Arg10]kallidin	Full agonist	7.6	pKi
[Leu8,des-Arg9]bradykinin	Antagonist	7.2	pKi
Met-Lys-bradykinin	Full agonist	7.1	pIC50
JMV1431	Antagonist	7.1	pKi

Binding affinities (BindingDB)

45 measured of 47 human assays (47 total across all organisms); most potent 45 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[3-[[(1R)-1-[4-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-2-methoxypyrimidine-5-carboxamide	KI	0.6 nM	US-8912221: Biaryl amide derivatives
methyl 2-chloro-6-[3-fluoro-4-[(1R)-1-[[3-(1,2-oxazole-5-carbonylamino)oxetane-3-carbonyl]amino]ethyl]phenyl]benzoate	KI	0.8 nM	US-8912221: Biaryl amide derivatives
methyl 2-chloro-6-[3-fluoro-4-[(1R)-1-[[3-[(3-methyl-1,2-oxazole-5-carbonyl)amino]oxetane-3-carbonyl]amino]ethyl]phenyl]benzoate	KI	1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-3-methyl-1,2-oxazole-5-carboxamide	KI	1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]pyridazine-4-carboxamide	KI	1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]pyrimidine-5-carboxamide	KI	1.1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-2-methoxypyrimidine-5-carboxamide	KI	1.1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-2-methoxypyrimidine-5-carboxamide	KI	1.1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-2-methoxypyrimidine-5-carboxamide	KI	1.1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-3-methyl-1,2-oxazole-5-carboxamide	KI	1.2 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-2-methoxypyrimidine-5-carboxamide	KI	1.2 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]pyridine-3-carboxamide	KI	1.3 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-3-methoxy-1,2-oxazole-5-carboxamide	KI	1.4 nM	US-8912221: Biaryl amide derivatives
5-amino-N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]pyridine-3-carboxamide	KI	1.4 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-3-methoxy-1,2-oxazole-5-carboxamide	KI	1.4 nM	US-8912221: Biaryl amide derivatives
methyl 2-chloro-6-[3-fluoro-4-[(1R)-1-[[3-(pyrimidine-5-carbonylamino)oxetane-3-carbonyl]amino]ethyl]phenyl]benzoate	KI	1.6 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-4-methylthiadiazole-5-carboxamide	KI	1.6 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-3-methyl-1,2-oxazole-5-carboxamide	KI	1.6 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[4-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-2-fluorophenyl]ethyl]-3-[(2,2,2-trifluoroacetyl)amino]oxetane-3-carboxamide	KI	1.7 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-3-methoxy-1,2-oxazole-5-carboxamide	KI	2.2 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-1,2-oxazole-5-carboxamide	KI	2.3 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-1,2-oxazole-5-carboxamide	KI	2.4 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-3-methyl-1,2-oxazole-5-carboxamide	KI	2.5 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]-3-[[3-fluoro-5-(trifluoromethyl)benzoyl]amino]oxetane-3-carboxamide	KI	2.6 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]pyrimidine-5-carboxamide	KI	2.6 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-3-methoxy-1,2-oxazole-5-carboxamide	KI	3 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-2-methoxypyrimidine-5-carboxamide	KI	3.3 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-3-methoxy-1,2-oxazole-5-carboxamide	KI	3.5 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]-3-[(2,2,2-trifluoroacetyl)amino]oxetane-3-carboxamide	KI	4.3 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[4-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-2-fluorophenyl]ethyl]carbamoyl]oxetan-3-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide	KI	4.3 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-1,2-oxazole-5-carboxamide	KI	4.7 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-3-methyl-1,2-oxazole-5-carboxamide	KI	5.1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide	KI	5.1 nM	US-8912221: Biaryl amide derivatives
methyl 2-chloro-6-[3-fluoro-4-[(1R)-1-[[3-(3,3,3-trifluoropropanoylamino)oxetane-3-carbonyl]amino]ethyl]phenyl]benzoate	KI	5.3 nM	US-8912221: Biaryl amide derivatives
methyl 2-chloro-6-[3-fluoro-4-[(1R)-1-[[3-[(2,2,2-trifluoroacetyl)amino]oxetane-3-carbonyl]amino]ethyl]phenyl]benzoate	KI	6.5 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-4-methylthiadiazole-5-carboxamide	KI	7.1 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide	KI	8.7 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]-3-[(2,2,2-trifluoroacetyl)amino]oxetane-3-carboxamide	KI	11.9 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]pyridazine-3-carboxamide	KI	14.1 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[4-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-2-fluorophenyl]ethyl]-3-[(2,2,2-trifluoroacetyl)amino]oxetane-3-carboxamide	KI	19.9 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]-3-[(2-methoxyacetyl)amino]oxetane-3-carboxamide	KI	25 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-1-methylimidazole-4-carboxamide	KI	82.6 nM	US-8912221: Biaryl amide derivatives
N-[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]-3-[(2-methoxyacetyl)amino]oxetane-3-carboxamide	KI	119 nM	US-8912221: Biaryl amide derivatives
N-[3-[[(1R)-1-[5-[5-chloro-3-fluoro-2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]oxetan-3-yl]-1-methylimidazole-2-carboxamide	KI	503 nM	US-8912221: Biaryl amide derivatives
CAS_167710-87-4	KI	794 nM

ChEMBL bioactivities

1145 potent at pChembl≥5 of 1151 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL160547
10.82	Kd	0.015	nM	CHEMBL359553
10.70	Ki	0.02	nM	CHEMBL359553
10.70	Ki	0.02	nM	CHEMBL185693
10.64	Ki	0.023	nM	CHEMBL3085458
10.52	Ki	0.03	nM	CHEMBL189123
10.47	Ki	0.034	nM	CHEMBL189123
10.46	Ki	0.035	nM	CHEMBL3142391
10.42	Ki	0.038	nM	CHEMBL189123
10.40	IC50	0.04	nM	CHEMBL359553
10.35	Ki	0.045	nM	CHEMBL425588
10.35	Ki	0.045	nM	CHEMBL1939755
10.31	Ki	0.049	nM	CHEMBL189123
10.30	Ki	0.05	nM	CHEMBL425588
10.15	Ki	0.07	nM	CHEMBL185811
10.15	Ki	0.07	nM	CHEMBL185727
10.12	IC50	0.075	nM	CHEMBL394370
10.10	Ki	0.08	nM	CHEMBL425588
10.08	IC50	0.084	nM	CHEMBL1939758
10.05	IC50	0.09	nM	CHEMBL1834752
10.00	IC50	0.1	nM	CHEMBL3648475
10.00	IC50	0.1	nM	CHEMBL3648480
10.00	Ki	0.1	nM	CHEMBL504531
10.00	Ki	0.1	nM	CHEMBL1777956
10.00	Ki	0.1	nM	CHEMBL1777957
10.00	Ki	0.1	nM	CHEMBL1777958
9.96	Ki	0.11	nM	CHEMBL1777969
9.94	IC50	0.115	nM	CHEMBL1939755
9.92	IC50	0.12	nM	CHEMBL502140
9.92	Ki	0.12	nM	CHEMBL1777955
9.89	Ki	0.13	nM	CHEMBL373530
9.89	IC50	0.13	nM	CHEMBL609157
9.85	IC50	0.14	nM	CHEMBL447870
9.85	IC50	0.14	nM	CHEMBL604735
9.85	IC50	0.14	nM	CHEMBL1777969
9.82	Ki	0.15	nM	CHEMBL450541
9.82	Ki	0.15	nM	CHEMBL1777954
9.80	Ki	0.16	nM	CHEMBL1777958
9.77	Ki	0.17	nM	CHEMBL1777879
9.74	IC50	0.18	nM	CHEMBL189123
9.74	Ki	0.18	nM	CHEMBL1777968
9.74	IC50	0.18	nM	CHEMBL1834619
9.72	Ki	0.19	nM	CHEMBL502140
9.72	IC50	0.19	nM	CHEMBL599285
9.71	Ki	0.197	nM	CHEMBL1939758
9.70	Ki	0.2	nM	CHEMBL2087422
9.70	IC50	0.2	nM	CHEMBL3648476
9.70	IC50	0.2	nM	CHEMBL3648488
9.70	IC50	0.2	nM	CHEMBL3648489
9.70	IC50	0.2	nM	CHEMBL3648490

PubChem BioAssay actives

1010 with measured affinity, of 1709 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-[(2R)-7-chloro-1-naphthalen-2-ylsulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[2-[4-(1-methyl-4,5-dihydroimidazol-2-yl)phenyl]ethyl]acetamide	239603: Binding affinity to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay	ki	<0.0001	uM
2-[(2R)-7-chloro-1-naphthalen-2-ylsulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl]acetamide	239603: Binding affinity to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay	ki	<0.0001	uM
2-[(3R)-4-(4-methylphenyl)sulfonyl-2-oxo-1,3-dihydropyrazin-3-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	640243: Displacement of [3H]-DAK from human bradykinin B1 receptor expressed in CHO-D-/aequorin cells membrane after 90 mins by scintillation counting	ki	<0.0001	uM
methyl 2-fluoro-6-[3-fluoro-4-[[[5-(4-pyridin-4-ylpiperazine-1-carbonyl)-2-pyridinyl]amino]methyl]phenyl]benzoate	264062: Binding affinity to human BK1 receptor	ki	<0.0001	uM
N-[2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl]-2-[(2R)-1-naphthalen-2-ylsulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]acetamide	238159: Equilibrium dissociation constant of the [35S]- radiolabeled compound against human Bradykinin receptor B1 expressed in CHO membranes was determined	kd	<0.0001	uM
2-[(3S)-3-[[(2S)-2-[[(2S)-2-[[2-[[(2S,4R)-1-[(2S)-1-[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-2-(2,3-dihydro-1H-inden-2-yl)acetyl]amino]-3-hydroxypropanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetic acid	42993: Ability to bind to human cloned B1 receptor in competition binding experiments with [3H][des-Arg10,Leu9]-Kallidin.	ki	<0.0001	uM
2-[(3S)-3-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2R)-2-[[(2S)-6-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-2-(2,3-dihydro-1H-inden-2-yl)acetyl]amino]-3-hydroxypropanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetic acid	42993: Ability to bind to human cloned B1 receptor in competition binding experiments with [3H][des-Arg10,Leu9]-Kallidin.	ki	<0.0001	uM
2-[(2R)-1-(3,4-dichlorophenyl)sulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[2-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]ethyl]acetamide	239603: Binding affinity to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay	ki	<0.0001	uM
methyl 2-fluoro-6-[3-fluoro-4-[(1R)-1-[[1-(3,3,3-trifluoropropanoylamino)cyclopropanecarbonyl]amino]ethyl]phenyl]benzoate	275642: Displacement of [3H]des-Arg10 Leu9 kallidin from human bradykinin B1 receptor expressed in CHO cells	ki	0.0001	uM
N-[2-[4-(1H-imidazol-2-yl)phenyl]ethyl]-2-[(2R)-1-naphthalen-2-ylsulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]acetamide	239603: Binding affinity to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay	ki	0.0001	uM
4-bromo-3-[(2-chlorobenzoyl)amino]-N-[4-[2-(4,5-dihydro-1H-imidazol-2-yl)ethyl]phenyl]-1H-pyrazole-5-carboxamide	298458: Antagonist activity at human bradykinin B1 receptor in IL1-beta stimulated IMR90 cells by FLIPR assay	ic50	0.0001	uM
2-[3-oxo-1-[3-(trifluoromethyl)phenyl]sulfonylpiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0001	uM
2-[1-[(5-chloro-1-benzothiophen-2-yl)sulfonyl]-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0001	uM
2-[1-(3-bromo-5-chlorothiophen-2-yl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0001	uM
2-[(2R)-7-chloro-1-naphthalen-2-ylsulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[2-[4-(1H-imidazol-2-yl)phenyl]ethyl]acetamide	239603: Binding affinity to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay	ki	0.0001	uM
2-[(2R)-1-(benzenesulfonyl)-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[(4R)-7-(piperidin-1-ylmethyl)-3,4-dihydro-2H-chromen-4-yl]acetamide	362203: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells	ic50	0.0001	uM
2-[1-[4-methyl-3-(trifluoromethyl)phenyl]sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0001	uM
2-[(2R)-1-(3,4-dichlorophenyl)sulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[(4R)-7-(piperidin-1-ylmethyl)-3,4-dihydro-2H-chromen-4-yl]acetamide	362202: Displacement of [3H]DAK from human bradykinin B1 receptor expressed in CHO-D-/aequorin cells by rapid filtration technique	ki	0.0001	uM
2-[(2R)-1-(3,4-dichlorophenyl)sulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	362202: Displacement of [3H]DAK from human bradykinin B1 receptor expressed in CHO-D-/aequorin cells by rapid filtration technique	ki	0.0001	uM
2-[(2R)-1-(4-methylphenyl)sulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]-N-[(4R)-7-(piperidin-1-ylmethyl)-3,4-dihydro-2H-chromen-4-yl]acetamide	362203: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells	ic50	0.0001	uM
3-[[4-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-2-fluorophenyl]methyl]-1-ethyl-1-[(3-methoxy-1,2-oxazole-5-carbonyl)amino]urea	461327: Antagonist activity at bradykinin B1 receptor in human IMR90 cells assessed as inhibition of des-Arg-bradykinin-mediated calcium mobilization	ic50	0.0001	uM
3-[(1R)-1-[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]ethyl]-1-ethyl-1-[(3-methoxy-1,2-oxazole-5-carbonyl)amino]urea	461327: Antagonist activity at bradykinin B1 receptor in human IMR90 cells assessed as inhibition of des-Arg-bradykinin-mediated calcium mobilization	ic50	0.0001	uM
2-[(2R)-1-(4-methylphenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	622673: Antagonist activity at human B1 receptor	ki	0.0001	uM
2-[(2R)-1-(4-methylphenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-[(4-methylpiperidin-1-yl)methyl]-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598458: Antagonist activity at human bradykinin B1 receptor expressed in CHO cells assessed as inhibition of agonist-induced calcium efflux by aquerin based assay	ic50	0.0001	uM
6-(8-fluoro-4-methyl-1-oxophthalazin-2-yl)-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]pyridine-3-carboxamide	622675: Antagonist activity at human B1 receptor expressed in CHO cells by aequorin-based calcium flux assay	ic50	0.0001	uM
2-[(3R)-4-(4-methylphenyl)sulfonyl-2-oxo-1,3-dihydropyrazin-3-yl]-N-[(1R)-6-(pyrrolidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	640244: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells assessed as inhibition of DAK-induced intracellular calcium level after 1.5 to 2 hrs by luminometry analysis	ic50	0.0001	uM
N-[2-[2-[4-(1-ethylpiperidin-4-yl)piperazin-1-yl]-2-oxoethoxy]ethyl]-4-methoxy-N,2,6-trimethylbenzenesulfonamide	684574: Displacement of [3H]des-Arg10-KD from human recombinant B1 receptor expressed in HEK293 cells by liquid scintillation counter	ki	0.0002	uM
2-[(2R)-1-(4-chlorophenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598458: Antagonist activity at human bradykinin B1 receptor expressed in CHO cells assessed as inhibition of agonist-induced calcium efflux by aquerin based assay	ic50	0.0002	uM
3-chloro-N-[1-[[(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoro-2-pyridinyl]ethyl]carbamoyl]cyclopropyl]-1,2-oxazole-5-carboxamide	315797: Binding affinity to human bradykinin B1 receptor expressed in rat CNS	ki	0.0002	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	239710: Binding affinity (radioligand) to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay; value ranges from 0.1-0.2 nM	ki	0.0002	uM
oxolan-2-ylmethyl N-[4-[[2-(5-fluoropyridine-2-carbonyl)phenyl]sulfamoyl]phenyl]carbamate	339348: Binding affinity to human bradykinin B1 receptor	ki	0.0002	uM
(3R)-3-(naphthalen-2-ylsulfonylamino)-3-phenyl-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]propanamide	277185: Displacement of [3H]DAK from human bradykinin B1 receptor expressed in CHO-D cells	ki	0.0002	uM
2-[(3S)-3-[[(2S)-2-[[2-[[2-[[(2S)-1-[(2S)-1-[(2R)-2-(2,6-diaminohexanoylamino)-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetic acid	42993: Ability to bind to human cloned B1 receptor in competition binding experiments with [3H][des-Arg10,Leu9]-Kallidin.	ki	0.0002	uM
N-[(1R)-1-[4-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-2-fluorophenyl]ethyl]-1-[(2,2,2-trifluoroacetyl)amino]cyclopropane-1-carboxamide	315797: Binding affinity to human bradykinin B1 receptor expressed in rat CNS	ki	0.0002	uM
3-[[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]methyl]-1-(4,4-difluorocyclohexyl)-1-hydroxyurea	459453: Antagonist activity at bradykinin B1 receptor in human IMR90 cells assessed as inhibition of des-Arg-bradykinin-mediated calcium mobilization	ic50	0.0002	uM
3-[[5-[5-chloro-3-fluoro-2-(2-methyltetrazol-5-yl)phenyl]-3-fluoro-2-pyridinyl]methyl]-1-ethyl-1-[(3-methoxy-1,2-oxazole-5-carbonyl)amino]urea	461327: Antagonist activity at bradykinin B1 receptor in human IMR90 cells assessed as inhibition of des-Arg-bradykinin-mediated calcium mobilization	ic50	0.0002	uM
2-[1-(3,4-dichlorophenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0002	uM
2-[1-(2,4-dichlorophenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0002	uM
2-[(2R)-1-(4-methylphenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(4R)-7-(piperidin-1-ylmethyl)-3,4-dihydro-2H-chromen-4-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0002	uM
N-[(1R)-6-[(cyclopropylmethylamino)methyl]-1,2,3,4-tetrahydronaphthalen-1-yl]-2-[(2R)-1-(4-methylphenyl)sulfonyl-3-oxopiperazin-2-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0002	uM
6-(8-chloro-4-methyl-1-oxophthalazin-2-yl)-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]pyridine-3-carboxamide	622675: Antagonist activity at human B1 receptor expressed in CHO cells by aequorin-based calcium flux assay	ic50	0.0002	uM
N-[(4S)-1-cyclopentyl-3,3-dimethylpiperidin-4-yl]-2-[(3R)-4-(4-methylphenyl)sulfonyl-2-oxo-1,3-dihydropyrazin-3-yl]acetamide	640244: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells assessed as inhibition of DAK-induced intracellular calcium level after 1.5 to 2 hrs by luminometry analysis	ic50	0.0002	uM
2-[(3R)-4-(2,3-dichlorophenyl)sulfonyl-2-oxo-1,3-dihydropyrazin-3-yl]-N-[(4S)-1,3,3-trimethylpiperidin-4-yl]acetamide	640244: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells assessed as inhibition of DAK-induced intracellular calcium level after 1.5 to 2 hrs by luminometry analysis	ic50	0.0002	uM
N-[(1R)-6-[(dimethylamino)methyl]-1,2,3,4-tetrahydronaphthalen-1-yl]-2-[(3R)-4-(4-methylphenyl)sulfonyl-2-oxo-1,3-dihydropyrazin-3-yl]acetamide	640244: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells assessed as inhibition of DAK-induced intracellular calcium level after 1.5 to 2 hrs by luminometry analysis	ic50	0.0002	uM
N-[(1R)-6-[(cyclopropylamino)methyl]-1,2,3,4-tetrahydronaphthalen-1-yl]-2-[(3R)-4-(4-methylphenyl)sulfonyl-2-oxo-1,3-dihydropyrazin-3-yl]acetamide	640244: Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells assessed as inhibition of DAK-induced intracellular calcium level after 1.5 to 2 hrs by luminometry analysis	ic50	0.0002	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-2-tritiopyrrolidine-2-carbonyl]-2-tritiopyrrolidine-2-carbonyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoic acid	239710: Binding affinity (radioligand) to human Bradykinin receptor B1 over-expressed in transgenic rats was determined by ex vivo receptor occupancy assay; value ranges from 0.1-0.2 nM	ki	0.0002	uM
2-[1-(4-methylphenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598458: Antagonist activity at human bradykinin B1 receptor expressed in CHO cells assessed as inhibition of agonist-induced calcium efflux by aquerin based assay	ic50	0.0003	uM
2-[(2R)-1-(4-methylphenyl)sulfonyl-3-oxopiperazin-2-yl]-N-[(1R)-6-[(2-methylpropylamino)methyl]-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide	598460: Antagonist activity at human bradykinin B1 receptor	ki	0.0003	uM
methyl 2-[4-[(1R)-1-[[4-chloro-3-[(2-cyanoacetyl)amino]-2-pyridinyl]amino]ethyl]phenyl]-6-fluorobenzoate	281948: Antagonist activity at bradykinin B1 receptor expressed in CHO cells assessed as inhibition of des-arg10-kallidin-induced increase in cytosolic calcium level by FLIPR assay	ic50	0.0003	uM
7-chloro-2-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)phenyl]-3H-isoindol-1-one	514938: Displacement of [3H]Lys0-des-Arg9-BK at human bradykinin B1 receptor expressed in HEK293 cells	ki	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
kallidin, des-Arg(10)-	increases abundance, increases activity, affects binding, increases reaction, affects reaction (+1 more)	3
Progesterone	affects cotreatment, decreases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance	2
Silicon Dioxide	decreases expression, increases expression	2
dexamethasone 21-phosphate	increases reaction, affects binding, decreases reaction	1
lead acetate	increases expression	1
quercitrin	decreases expression	1
arsenite	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
15-acetyldeoxynivalenol	increases expression	1
chromium hexavalent ion	decreases expression	1
anandamide	decreases activity, decreases reaction	1
bradykinin, Lys-Leu(8)-desArg(9)-	decreases reaction, increases activity	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
methanandamide	decreases activity	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate	decreases reaction, increases abundance, increases activity	1
AM 251	decreases activity, decreases reaction	1
abrine	increases expression	1
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate	decreases reaction, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1

ChEMBL screening assays

167 unique, capped per target: 113 binding, 51 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000163	Binding	Binding affinity to bradykinin 2 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1005610	Functional	Antagonist activity at human bradykinin B1 receptor expressed in CHO-D-/aequorin cells	Discovery of dihydroquinoxalinone acetamides containing bicyclic amines as potent Bradykinin B1 receptor antagonists. — Bioorg Med Chem Lett
CHEMBL853768	ADMET	Plasma concentration in hB1 knock-in-mouse at 6 mg/kg, po after 1 hr	Development of orally bioavailable and CNS penetrant biphenylaminocyclopropane carboxamide bradykinin B1 receptor antagonists. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H402	CHO-K1/B1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KB32	GeneBLAzer BDKRB1-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KU50	CHO-K1 BDKRB1 Gq	Spontaneously immortalized cell line	Female
CVCL_KW40	PathHunter CHO-K1 BDKRB1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_YK02	HEK293 BDKRB1 HiTSeeker	Transformed cell line	Female

Clinical trials (associated diseases)

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