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apelin receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 36

Nomenclature: apelin receptor

Family: Apelin receptor

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 380 11q12.1 APLNR apelin receptor 38
Mouse 7 377 2 D Aplnr apelin receptor 11
Rat 7 377 3q24 Aplnr apelin receptor 17,37
Previous and Unofficial Names Click here for help
angiotensin receptor-like 1 | AGTRL1 | APJ | APJR | angiotensin II receptor-like 1 | B78 | GPCR34 | G-protein coupled receptor APJ | msr/apj
Database Links Click here for help
Specialist databases
GPCRdb apj_human (Hs), apj_mouse (Mm), apj_rat (Rn)
Other databases
Alphafold P35414 (Hs), Q9WV08 (Mm), Q9JHG3 (Rn)
ChEMBL Target CHEMBL1628481 (Hs), CHEMBL4879524 (Mm), CHEMBL2398 (Rn)
Ensembl Gene ENSG00000134817 (Hs), ENSMUSG00000044338 (Mm), ENSRNOG00000009227 (Rn)
Entrez Gene 187 (Hs), 23796 (Mm), 83518 (Rn)
Human Protein Atlas ENSG00000134817 (Hs)
KEGG Gene hsa:187 (Hs), mmu:23796 (Mm), rno:83518 (Rn)
OMIM 600052 (Hs)
Pharos P35414 (Hs)
RefSeq Nucleotide NM_005161 (Hs), NM_011784 (Mm), NM_031349 (Rn)
RefSeq Protein NP_005152 (Hs), NP_035914 (Mm), NP_112639 (Rn)
UniProtKB P35414 (Hs), Q9WV08 (Mm), Q9JHG3 (Rn)
Wikipedia APLNR (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human APJR in complex with a designed 17-amino-acid apelin mimetic peptide agonist, AMG3054.
PDB Id:  5VBL
Ligand:  AMG3054
Resolution:  2.6Å
Species:  Human
References:  27
Natural/Endogenous Ligands Click here for help
apelin-36 {Sp: Human}
apelin-13 {Sp: Human, Mouse, Rat}
apelin-17 {Sp: Human, Mouse, Rat}
apelin-36 {Sp: Mouse, Rat}
apelin receptor early endogenous ligand {Sp: Human} , apelin receptor early endogenous ligand {Sp: Mouse}
Elabela/Toddler-32 {Sp: Human}
Elabela/Toddler-21 {Sp: Human}
Elabela/Toddler-11 {Sp: Human}
[Pyr1]apelin-13 {Sp: Human, Mouse, Rat}
Potency order of endogenous ligands (Human)
[Pyr1]apelin-13 (APLN, Q9ULZ1) ≥ apelin-13 (APLN, Q9ULZ1) > apelin-36 (APLN, Q9ULZ1)  [13,46]

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I][Nle75,Tyr77]apelin-36 (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 11.2 pKd 21
⤷ pKd 11.2 (Kd 6.3x10-12 M) [21]
[125I][Glp65Nle75,Tyr77]apelin-13 Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 10.7 pKd 17
⤷ pKd 10.7 (Kd 2.23x10-11 M) [17]
BMS-986224 Small molecule or natural product Hs Agonist 10.5 pKd 14
⤷ pKd 10.5 (Kd 3x10-11 M) [14]
[125I](Pyr1)apelin-13 Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.5 pKd 20
⤷ pKd 9.5 (Kd 3x10-10 M) [20]
apelin receptor early endogenous ligand {Sp: Human} Peptide Primary target of this compound Ligand is endogenous in the given species Hs Agonist 9.3 pKd 10
⤷ pKd 9.3 (Kd 5.1x10-10 M) [10]
[125I]apelin-13 Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.2 pKd 13
⤷ pKd 9.2 (Kd 7x10-10 M) [13]
[3H](Pyr1)[Met(0)11]-apelin-13 Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.6 pKd 35
⤷ pKd 8.6 (Kd 2.7x10-9 M) [35]
compound 39 [PMID: 34982553] Small molecule or natural product Hs Agonist 9.2 pKi 48
⤷ pKi 9.2 (Ki 6x10-10 M) [48]
Description: Binding affinity
compound 40 [PMID: 34982553] Small molecule or natural product Hs Agonist 8.2 pKi 48
⤷ pKi 8.2 (Ki 5.7x10-9 M) [48]
Description: Binding affinity
E339-3D6 Small molecule or natural product Hs Agonist 6.4 pKi 19
⤷ pKi 6.4 [19]
compound 14a [PMID: 34795866] Small molecule or natural product Rn Agonist 10.5 pEC50 40
⤷ pEC50 10.5 (EC50 3.5x10-11 M) [40]
compound 21 [PMID: 34855405] Small molecule or natural product Hs Agonist 10.2 pEC50 36
⤷ pEC50 10.2 (EC50 6x10-11 M) [36]
Description: Determined in a homogeneous time-resolved fluorescence (HTRF) intracellular cAMP accumulation assay
compound 15a Small molecule or natural product Hs Agonist 10.0 pEC50 43
⤷ pEC50 10.0 (EC50 9.3x10-11 M) [43]
Description: Determined in an intracellular cAMP accumulation assay (hTR-FRET) using HEK293 cells stably expressing hAPLNR.
CMF-019 Small molecule or natural product Hs Biased agonist 10.0 pEC50 41
⤷ pEC50 10.0 [41]
Conditions: For in vivo studies the potassium salt of this compound was used.
compound 14a [PMID: 34795866] Small molecule or natural product Hs Agonist 9.6 pEC50 40
⤷ pEC50 9.6 (EC50 2.7x10-10 M) [40]
MM07 Peptide Hs Biased agonist 9.5 pEC50 4
⤷ pEC50 9.5 [4]
azelaprag Small molecule or natural product Hs Agonist 9.5 pEC50 2,6
⤷ pEC50 9.5 (EC50 3.2x10-10 M) [2,6]
Description: Measuring ligand-induced [35S]GTPyS Binding in membranes prepared fron CHO cells stably expressing human apelin receptor.
compound 1 [PMID: 25241924] Peptide Hs Full agonist 7.5 pEC50 34
⤷ pEC50 7.5 (EC50 3.37x10-8 M) [34]
cyclo apelin-12 (7-12) Peptide Hs Full agonist 7.1 pEC50 16
⤷ pEC50 7.1 (EC50 7.862x10-8 M) [16]
cyclourea apelin-12 (1-7) Peptide Hs Full agonist 6.8 pEC50 16
⤷ pEC50 6.8 (EC50 1.443x10-7 M) [16]
cyclo apelin-12 (1-12) Peptide Hs Full agonist 6.3 pEC50 16
⤷ pEC50 6.3 (EC50 4.932x10-7 M) [16]
ML233 Small molecule or natural product Hs Full agonist 5.4 pEC50 22
⤷ pEC50 5.4 (EC50 3.74x10-6 M) [22]
apelin-13 {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 8.8 – 9.5 pIC50 13,17,35
⤷ pIC50 8.8 – 9.5 [13,17,35]
Elabela/Toddler-32 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Agonist 8.7 pIC50 49
⤷ pIC50 8.7 [49]
Elabela/Toddler-21 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Agonist 8.7 pIC50 49
⤷ pIC50 8.7 [49]
apelin-17 {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Agonist 7.9 – 9.0 pIC50 12,35
⤷ pIC50 7.9 – 9.0 [12,35]
apelin-36 {Sp: Human} Peptide Primary target of this compound Ligand is endogenous in the given species Hs Full agonist 8.2 – 8.6 pIC50 13,17,21,35
⤷ pIC50 8.2 – 8.6 [13,17,21,35]
[Pyr1]apelin-13 {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 7.0 – 8.8 pIC50 21,35
⤷ pIC50 7.0 – 8.8 [21,35]
Elabela/Toddler-11 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Agonist 7.2 pIC50 49
⤷ pIC50 7.2 [49]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MM54 Peptide Hs Antagonist 8.2 pKi 28
⤷ pKi 8.2 (Ki 7.1x10-9 M) [28]
ALX40-4C Peptide Click here for species-specific activity table Hs Antagonist 5.5 pIC50 50
⤷ pIC50 5.5 [50]
ML221 Small molecule or natural product Hs Antagonist - - 29
⤷ [29]
Antagonist Comments
ALX40-4C is also an antagonist of the chemokine receptor CXCR4 and binds to the second extracellular loop of this receptor.
(Ala13)-apelin-13 is the first reported functional antagonist that blocks the hypotensive actions of apelin in a dose dependent manner. However, pIC50 values were not reported in this study [26].

Binding data for antagonist ML221 are not available [29].
Immunopharmacology Comments
The apelin receptor gene (APLNR) has been identified as one of a number of genes necessary to confer suceptibility of cancer cells to immunotherapy (i.e. T cell recognition and cytolysis) [39]. This effect is likely mediated by apelin receptor/JAK1 upregulation of the IFN-γ response that appears to promote antigen processing and presentation by tumours, and which improves the ability of T cells to recognize and attack the cancer cells. Defects in IFN-γ signalling is a recognised mechanism underlying resistance to immunotherapy [30]. The authors of [39] show that functional loss of APLNR in mouse models reduces the efficacy of immunotherapies (both adoptive cell transfer and checkpoint blockade) and is indicative of poor prognosis.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Comments:  Downstream of Gi activation apelin triggers a sharp increase in intracellular Ca2+ levels and activates ERKs via a PKC dependent pathway. Apelin dependent activation of ERK and PI3Kinase leads to activation of p70S6 kinase in endothelial cells.
References:  8,15,17,32-33
Tissue Distribution Click here for help
Adrenal gland: endothelial cells of surrounding arteries, small resistance arteries within the capsular plexus and central vein.
Species:  Human
Technique:  immunocytochemistry.
References:  24
Neurones and oligodendrocytes > astrocytes.
Not found in primary microglia or monocyte-derived macrophages.
Species:  Human
Technique:  immunocytochemistry.
References:  8
Heart, coronary artery, aorta, internal mammary artery, pulmonary artery and saphenous vein.
Species:  Human
Technique:  Radioligand binding.
References:  20
Heart: endothelial cells lining the intramyocardial vessels, small coronary arteries, endocardial endothelial cells > cardiomyocytes, vascular smooth muscle cells of cardiac blood vessels.
Species:  Human
Technique:  immunocytochemistry.
References:  24
Lung: endothelial cells of small pulmonary vessels > vascular smooth muscle cells of pulmonary vessels.
Not found in the alveolar epithelium or connective tissue.
Species:  Human
Technique:  immunocytochemistry.
References:  24
Kidney: Endothelial cells and vascular smooth muscle cells of small intrarenal vessels.
Not found in the glomerulli, renal tubular epithelial cells or connective tissue.
Species:  Human
Technique:  immunocytochemistry.
References:  24
Large conduit vessels: endothelial cells lining walls of saphenous veins, coronary arteries, radial arteries and left internal mammary arteries and vascular smooth muscle cells forming vessel walls.
Species:  Human
Technique:  immunocytochemistry.
References:  24
Brain: neurones of the lateral cerebellar nucleus > endothelial and vascular smooth muscle cells from small cerebellar vessels.
Species:  Rat
Technique:  immunocytochemistry.
References:  24
Lung: Bronchial epithelial cells > endothelial and vascular smooth muscle cells from pulmonary vessels.
Species:  Rat
Technique:  immunocytochemistry.
References:  24
Heart: Endothelial and vascular smooth muscle cells from small intramyocardial vessels > cardiomyocytes.
Species:  Rat
Technique:  immunocytochemistry.
References:  24
Vascular smooth muscle of the medial layer of rat aorta and pulmonary artery.
Species:  Rat
Technique:  immunocytochemistry.
References:  24
Cerebellum, lung, heart, kidney cortex.
Species:  Rat
Technique:  Radioligand binding.
References:  20
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Inhibition of HIV infection in CD4 positive cell lines expressing APJ.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of HIV infection.
References:  50
Measurement of cAMP levels in CHO cells transfected with the APJ receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-induced cAMP formation.
References:  15,21
Measurement of cAMP levels in HRK 293 cells transfected with the human APJ receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of forskolin-induced cAMP accumulation.
References:  35
Measurement of Ca2+ levels in RBL-2H3 cells transfected with the human APJ receptor using a fluorimetric imaging plate reader (FLIPR).
Species:  Human
Tissue:  RBL-2H3 cells.
Response measured:  Ca2+ mobilisation.
References:  35
Measurement of cAMP levels in CHO cells transfected with the rat APJ receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of forskolin-induced cAMP accumulation.
References:  42
Inhibition of HIV infection in CD4 positive cell lines expressing APJ.
Species:  Human
Tissue:  Cf2Th cells.
Response measured:  Inhibition of HIV infection.
References:  5
Inhibition of HIV infection in CD4 positive cell lines expressing APJ.
Species:  Human
Tissue:  NP-2 cells.
Response measured:  Inhibition of HIV infection.
References:  51
Physiological Functions Click here for help
Vasoconstriction.
Species:  Human
Tissue:  Saphenous vein.
References:  20
Vasodilation.
Species:  Rat
Tissue:  In vivo.
References:  7,25,42,47
Vasodilation.
Species:  Mouse
Tissue:  In vivo.
References:  18
Positive inotrope.
Species:  Rat
Tissue:  Isolated perfused heart.
References:  44
Positive inotrope.
Species:  Rat
Tissue:  In vivo.
References:  1,3
Modulation of water intake.
Species:  Rat
Tissue:  In vivo.
References:  9,25,42,45
Physiological Consequences of Altering Gene Expression Click here for help
In APJ receptor knockout mice baseline blood pressure is not changed compared to wild-type animals. Vasoconstrictor responses to angiotensin II however are significantly more pronounced in the knockout animals.
Species:  Human
Tissue: 
Technique:  Transgenesis.
References:  18
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0002332 abnormal exercise endurance PMID: 19767528 
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0000267 abnormal heart development PMID: 19767528 
Aplnr+|Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnr+
C57BL/6-Aplnr		 MGI:1346086  MP:0008779 abnormal maternal behavior PMID: 19767528 
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0008779 abnormal maternal behavior PMID: 19767528 
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0004215 abnormal myocardial fiber physiology PMID: 19767528 
Aplnrtm1Afu Aplnrtm1Afu/Aplnrtm1Afu
involves: C57BL/6 * CBA		 MGI:1346086  MP:0000230 abnormal systemic arterial blood pressure PMID: 15087458 
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0005140 decreased cardiac muscle contractility PMID: 19767528 
Aplnr+|Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnr+
C57BL/6-Aplnr		 MGI:1346086  MP:0001935 decreased litter size PMID: 19767528 
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0001730 embryonic growth arrest PMID: 19767528 
Aplnrtm1.1Tq Aplnrtm1.1Tq/Aplnrtm1.1Tq
C57BL/6-Aplnr		 MGI:1346086  MP:0002080 prenatal lethality PMID: 19767528 
General Comments
The biology of the apelin receptor system has recently been comprehensively reviewed in the works of Kleinz et al. (2005) and Masri et al. (2005) [23,31].

References

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1. Ashley EA, Powers J, Chen M, Kundu R, Finsterbach T, Caffarelli A, Deng A, Eichhorn J, Mahajan R, Agrawal R et al.. (2005) The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res, 65 (1): 73-82. [PMID:15621035]

2. Ason B, Chen Y, Guo Q, Hoagland KM, Chui RW, Fielden M, Sutherland W, Chen R, Zhang Y, Mihardja S et al.. (2020) Cardiovascular response to small-molecule APJ activation. JCI Insight, 5 (8). [PMID:32208384]

3. Berry MF, Pirolli TJ, Jayasankar V, Burdick J, Morine KJ, Gardner TJ, Woo YJ. (2004) Apelin has in vivo inotropic effects on normal and failing hearts. Circulation, 110 (11 Suppl 1): II187-93. [PMID:15364861]

4. Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP. (2015) Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist. Hypertension, 65 (4): 834-40. [PMID:25712721]

5. Cayabyab M, Hinuma S, Farzan M, Choe H, Fukusumi S, Kitada C, Nishizawa N, Hosoya M, Nishimura O, Messele T et al.. (2000) Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J Virol, 74 (24): 11972-6. [PMID:11090199]

6. Chen N, Chen X, Chen Y, Cheng AC, Connors RV, Deignan J, Dransfield PJ, Du X, Fu Z, Heath JA et al.. (2016) Triazole agonists of the apj receptor. Patent number: WO2016187308A1. Assignee: Amgen Inc.. Priority date: 20/05/2015. Publication date: 24/11/2016.

7. Cheng X, Cheng XS, Pang CC. (2003) Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ receptor, in conscious rats. Eur J Pharmacol, 470 (3): 171-5. [PMID:12798955]

8. Choe W, Albright A, Sulcove J, Jaffer S, Hesselgesser J, Lavi E, Crino P, Kolson DL. (2000) Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells. J Neurovirol, 6 Suppl 1: S61-9. [PMID:10871767]

9. De Mota N, Reaux-Le Goazigo A, El Messari S, Chartrel N, Roesch D, Dujardin C, Kordon C, Vaudry H, Moos F, Llorens-Cortes C. (2004) Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci USA, 101 (28): 10464-9. [PMID:15231996]

10. Deng C, Chen H, Yang N, Feng Y, Hsueh AJ. (2015) Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi Signaling. J Biol Chem, 290 (30): 18261-8. [PMID:25995451]

11. Devic E, Rizzoti K, Bodin S, Knibiehler B, Audigier Y. (1999) Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ. Mech Dev, 84 (1-2): 199-203. [PMID:10473142]

12. El Messari S, Iturrioz X, Fassot C, De Mota N, Roesch D, Llorens-Cortes C. (2004) Functional dissociation of apelin receptor signaling and endocytosis: implications for the effects of apelin on arterial blood pressure. J Neurochem, 90 (6): 1290-301. [PMID:15341513]

13. Fan X, Zhou N, Zhang X, Mukhtar M, Lu Z, Fang J, DuBois GC, Pomerantz RJ. (2003) Structural and functional study of the apelin-13 peptide, an endogenous ligand of the HIV-1 coreceptor, APJ. Biochemistry, 42 (34): 10163-8. [PMID:12939143]

14. Gargalovic P, Wong P, Onorato J, Finlay H, Wang T, Yan M, Crain E, St-Onge S, Héroux M, Bouvier M et al.. (2021) In Vitro and In Vivo Evaluation of a Small-Molecule APJ (Apelin Receptor) Agonist, BMS-986224, as a Potential Treatment for Heart Failure. Circ Heart Fail, 14 (3): e007351. [PMID:33663236]

15. Habata Y, Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Hinuma S, Kitada C, Nishizawa N, Murosaki S, Kurokawa T et al.. (1999) Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochim Biophys Acta, 1452 (1): 25-35. [PMID:10525157]

16. Hamada J, Kimura J, Ishida J, Kohda T, Morishita S, Ichihara S, Fukamizu A. (2008) Evaluation of novel cyclic analogues of apelin. Int J Mol Med, 22 (4): 547-52. [PMID:18813863]

17. Hosoya M, Kawamata Y, Fukusumi S, Fujii R, Habata Y, Hinuma S, Kitada C, Honda S, Kurokawa T, Onda H et al.. (2000) Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem, 275 (28): 21061-7. [PMID:10777510]

18. Ishida J, Hashimoto T, Hashimoto Y, Nishiwaki S, Iguchi T, Harada S, Sugaya T, Matsuzaki H, Yamamoto R, Shiota N et al.. (2004) Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. J Biol Chem, 279 (25): 26274-9. [PMID:15087458]

19. Iturrioz X, Alvear-Perez R, De Mota N, Franchet C, Guillier F, Leroux V, Dabire H, Le Jouan M, Chabane H, Gerbier R et al.. (2010) Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist. FASEB J, 24 (5): 1506-17. [PMID:20040517]

20. Katugampola SD, Maguire JJ, Matthewson SR, Davenport AP. (2001) [(125)I]-(Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man. Br J Pharmacol, 132 (6): 1255-60. [PMID:11250876]

21. Kawamata Y, Habata Y, Fukusumi S, Hosoya M, Fujii R, Hinuma S, Nishizawa N, Kitada C, Onda H, Nishimura O, Fujino M. (2001) Molecular properties of apelin: tissue distribution and receptor binding. Biochim Biophys Acta, 1538: 162-171. [PMID:11336787]

22. Khan P, Maloney PR, Hedrick M, Gosalia P, Milewski M, Li L, Roth GP, Sergienko E, Suyama E, Sugarman E et al.. (2011) Functional Agonists of the Apelin (APJ) Receptor. Probe Reports from the NIH Molecular Libraries Program,. [PMID:22834038]

23. Kleinz MJ, Davenport AP. (2005) Emerging roles of apelin in biology and medicine. Pharmacol Ther, 107 (2): 198-211. [PMID:15907343]

24. Kleinz MJ, Skepper JN, Davenport AP. (2005) Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells. Regul Pept, 126 (3): 233-40. [PMID:15664671]

25. Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, Osmond DH, George SR, O'Dowd BF. (2000) Characterization of apelin, the ligand for the APJ receptor. J Neurochem, 74 (1): 34-41. [PMID:10617103]

26. Lee DK, Saldivia VR, Nguyen T, Cheng R, George SR, O'Dowd BF. (2005) Modification of the terminal residue of apelin-13 antagonizes its hypotensive action. Endocrinology, 146 (1): 231-6. [PMID:15486224]

27. Ma Y, Yue Y, Ma Y, Zhang Q, Zhou Q, Song Y, Shen Y, Li X, Ma X, Li C et al.. (2017) Structural Basis for Apelin Control of the Human Apelin Receptor. Structure, 25 (6): 858-866.e4. [PMID:28528775]

28. Macaluso NJ, Pitkin SL, Maguire JJ, Davenport AP, Glen RC. (2011) Discovery of a competitive apelin receptor (APJ) antagonist. ChemMedChem, 6 (6): 1017-23. [PMID:21560248]

29. Maloney PR, Khan P, Hedrick M, Gosalia P, Milewski M, Li L, Roth GP, Sergienko E, Suyama E, Sugarman E et al.. (2012) Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor. Bioorg Med Chem Lett, 22 (21): 6656-60. [PMID:23010269]

30. Manguso RT, Pope HW, Zimmer MD, Brown FD, Yates KB, Miller BC, Collins NB, Bi K, LaFleur MW, Juneja VR et al.. (2017) In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature, 547 (7664): 413-418. [PMID:28723893]

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