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RXFP4

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Target not currently curated in GtoImmuPdb

Target id: 354

Nomenclature: RXFP4

Family: Relaxin family peptide receptors

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 7 374 1q22 RXFP4 relaxin family peptide/INSL5 receptor 4 23
Mouse 7 414 3 F1 Rxfp4 relaxin family peptide receptor 4 7
Gene and Protein Information Comments
Present in rats as a pseudogene.
Previous and Unofficial Names Click here for help
RLN3R2 | GPCR142 | INSL5 receptor | RXFPR4 | G protein-coupled receptor 100 | relaxin/insulin-like family peptide receptor 4 | relaxin/insulin like family peptide receptor 4
Database Links Click here for help
Specialist databases
GPCRdb rl3r2_human (Hs), rl3r2_mouse (Mm)
Other databases
Alphafold Q8TDU9 (Hs), Q7TQP4 (Mm)
ChEMBL Target CHEMBL1628473 (Hs)
Ensembl Gene ENSG00000173080 (Hs), ENSMUSG00000049741 (Mm)
Entrez Gene 339403 (Hs), 242093 (Mm)
Human Protein Atlas ENSG00000173080 (Hs)
KEGG Gene hsa:339403 (Hs), mmu:242093 (Mm)
OMIM 609043 (Hs)
Pharos Q8TDU9 (Hs)
RefSeq Nucleotide NM_181885 (Hs), NM_181817 (Mm)
RefSeq Protein NP_871001 (Hs), NP_861538 (Mm)
UniProtKB Q8TDU9 (Hs), Q7TQP4 (Mm)
Wikipedia RXFP4 (Hs)
Natural/Endogenous Ligands Click here for help
INSL5 {Sp: Human} , INSL5 {Sp: Mouse}
relaxin-3 {Sp: Human}
Potency order of endogenous ligands (Human)
INSL5 (INSL5, Q9Y5Q6) = relaxin-3 (RLN3, Q8WXF3) > relaxin-3 (B chain) (RLN3, Q8WXF3)  [22-23]

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]relaxin-3 (human) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 – 9.7 pKd 23
⤷ pKd 8.7 – 9.7 (Kd 2x10-9 – 2x10-10 M) [23]
[125I]relaxin-3-B/INSL5 A chimera Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist 8.9 pKd 22
⤷ pKd 8.9 (Kd 1.2x10-9 M) [22]
[125I]INSL5 (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.6 pKd 24
⤷ pKd 8.6 [24]
europium-labelled mouse INSL5 Peptide Ligand is labelled Mm Full agonist 8.6 pKd 4
⤷ pKd 8.6 [4]
europium-labelled relaxin-3-B/INSL5 A chimera Peptide Click here for species-specific activity table Ligand is labelled Hs Agonist 8.3 pKd 13
⤷ pKd 8.3 (Kd 5x10-9 M) [13]
europium-labelled mouse INSL5 Peptide Ligand is labelled Hs Agonist 8.3 pKd 5
⤷ pKd 8.3 (Kd 5x10-9 M) [5]
relaxin-3 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.8 – 9.0 pKi 18,23,29,45
⤷ pKi 9.0 [23,29]
pKi 8.8 – 8.8 [18,45]
R3/I5 Peptide Click here for species-specific activity table Hs Full agonist 8.9 pKi 18,39
⤷ pKi 8.9 [18,39]
INSL5 {Sp: Mouse} Peptide Ligand is endogenous in the given species Mm Full agonist 8.5 – 8.8 pKi 4,28
⤷ pKi 8.5 – 8.8 [4,28]
ΔR3/I5 Peptide Hs Agonist 8.3 pKi 29
⤷ pKi 8.3 [29]
INSL5 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.3 – 8.8 pKi 4,24,27-29,31,45
⤷ pKi 7.3 – 8.8 [4,24,27-29,31,45]
hINSL5: A8-21 (T15K) Peptide Hs Agonist 7.5 pKi 28
⤷ pKi 7.5 (Ki 2.951x10-8 M) [28]
hINSL5: A8-21 (T9R) Peptide Hs Full agonist 7.5 pKi 28
⤷ pKi 7.5 [28]
INSL5 analogue 13 Peptide Hs Agonist 7.5 pKi 29
⤷ pKi 7.5 [29]
minimised relaxin-3 analogue 2 Peptide Click here for species-specific activity table Hs Full agonist 7.1 pKi 29,31
⤷ pKi 7.1 [29,31]
INSL5 amide (mouse) Peptide Mm Full agonist 7.1 pKi 5
⤷ pKi 7.1 [5]
DC591053 Small molecule or natural product Ligand has a PDB structure Hs Agonist 6.9 pKi 8
⤷ pKi 6.9 (Ki 1.12x10-7 M) [8]
minimised INSL5 analogue 7 Peptide Hs Partial agonist 6.3 pKi 4
⤷ pKi 6.3 [4]
INSL5 amide (human) Peptide Hs Full agonist 5.0 – 6.9 pKi 5,27
⤷ pKi 5.0 – 6.9 [5,27]
relaxin-3 {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 8.7 – 9.7 pEC50 2,45
⤷ pEC50 8.7 – 9.7 [2,45]
R3/I5 Peptide Click here for species-specific activity table Hs Full agonist 8.9 pEC50 18
⤷ pEC50 8.9 [18]
compound 4 [PMID: 30824200] Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.8 pEC50 9
⤷ pEC50 8.8 (EC50 1.6x10-9 M) [9]
INSL5 {Sp: Mouse} Peptide Mm Full agonist 7.8 – 9.4 pEC50 2-3
⤷ pEC50 7.8 – 9.4 [2-3]
compound 10d [PMID: 34855388] Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.6 pEC50 12
⤷ pEC50 8.6 (EC50 2.7x10-9 M) [12]
Description: Receptor activation via cAMP assay
INSL5 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.0 – 8.9 pEC50 1,3,17,24
⤷ pEC50 7.0 – 8.9 [1,17,24]
pEC50 7.0 – 7.7 [3]
compound 7a [PMID: 33730669] Small molecule or natural product Hs Agonist 7.3 pEC50 21
⤷ pEC50 7.3 [21]
relaxin-3 (B chain) {Sp: Human} Peptide Click here for species-specific activity table Hs Partial agonist 7.0 pEC50 23
⤷ pEC50 7.0 [23]
JK1 Small molecule or natural product Hs Agonist 5.6 pEC50 20
⤷ pEC50 5.6 (EC50 2.63x10-6 M) [20]
Description: Determined in a pCRE reporter gene assay.
WNN0109-C011 Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.5 pEC50 19
⤷ pEC50 4.5 (EC50 3.388x10-5 M) [19]
Description: Determined in a cAMP accumulation assay
R3/I5 Peptide Click here for species-specific activity table Hs Agonist 10.5 pIC50 39
⤷ pIC50 10.5 [39]
INSL5 {Sp: Mouse} Peptide Ligand is endogenous in the given species Mm Full agonist 9.2 – 9.3 pIC50 2,4,28
⤷ pIC50 9.2 – 9.3 [2,4,28]
relaxin-3 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.8 – 9.0 pIC50 2,18,29
⤷ pIC50 8.8 – 9.0 [2,18,29]
INSL5 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.0 – 9.8 pIC50 1,4,24,27-29,31,41
⤷ pIC50 8.0 – 9.8 [1,4,24,27-29,31,41]
analogue 13: B7-24 Peptide Hs Agonist 8.1 pIC50 44
⤷ pIC50 8.1 [44]
minimised relaxin-3 analogue 2 Peptide Click here for species-specific activity table Hs Full agonist 7.7 pIC50 29,31
⤷ pIC50 7.7 [29,31]
hINSL5: A8-21 (T9R) Peptide Hs Full agonist 7.7 pIC50 28
⤷ pIC50 7.7 [28]
INSL5 analogue 13 Peptide Hs Agonist 7.7 pIC50 29
⤷ pIC50 7.7 [29]
INSL5 amide (human) Peptide Hs Full agonist 7.5 pIC50 5
⤷ pIC50 7.5 [5]
minimised INSL5 analogue 7 Peptide Hs Partial agonist 7.4 pIC50 4
⤷ pIC50 7.4 [4]
relaxin-3 (B chain) {Sp: Human} Peptide Click here for species-specific activity table Hs Partial agonist 6.9 – 7.1 pIC50 23-24
⤷ pIC50 6.9 – 7.1 [23-24]
INSL5 amide (mouse) Peptide Mm Full agonist 6.8 pIC50 5
⤷ pIC50 6.8 [5]
NanoLuc R3/I5 chimera Peptide Click here for species-specific activity table Ligand is labelled Hs Agonist - - 14,37
⤷ [14,37]
View species-specific agonist tables
Agonist Comments
Affinity values were determined in COS-7 cells expressing human RXFP4. Amidated peptides are much less potent than the native peptides. Mouse orthologues are generally more potent than the human peptide at human RXFP4 although recent studies suggest that this may be related to some extent to different purity of peptides rather than generic differences in potency. Although a potent agonist at RXFP4, relaxin-3 is unlikely to be a physiological ligand due to mismatch of expression patterns of peptide and receptor. In addition to inhibition of cAMP accumulation, RXFP4 is now known to cause phosphorylation of ERK1/2, p38MAPK, Akt Ser473 and Thr308, and S6RP [3].
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
R3(BΔ23-27)R/I5 chimeric peptide Peptide Click here for species-specific activity table Hs Antagonist 8.0 – 8.6 pIC50 13,18
⤷ pIC50 8.0 – 8.6 [13,18]
INSL5-A13NR Peptide Hs Antagonist 7.4 pIC50 30
⤷ pIC50 7.4 (IC50 3.98x10-8 M) [30]
minimised relaxin-3 analogue 3 Peptide Click here for species-specific activity table Hs Antagonist 6.6 pIC50 31
⤷ pIC50 6.6 [31]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Other - See Comments
Comments:  Phosphorylation of ERK1/2, p38MAPK, Akt Ser473 and Thr308, and S6RP [3].
References:  3,22-24
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Calcium channel
Other - See Comments
Comments:  Calcium signalling is only activated in cells co-expressing the promiscuous G protein Gα16. RXFP4 causes pERK1/2 activation in MIN6 and GLUTag cells in response to INSL5 in single dose studies, but also in CHO cells expressing RXFP4 in which p38MAPK, Akt and S6RP are also activated [3].
References:  3,24-25
Tissue Distribution Click here for help
Stomach, fetal brain, brain, leukocytes, kidney, colon, prostate, lung, ovary, thymus, thyroid, placenta, spleen, pituitary, heart.
Species:  Human
Technique:  RT-PCR.
References:  24
Colon, thyroid, salivary gland, prostate, placenta, thymus, testis, kidney, brain.
Species:  Human
Technique:  RT-PCR.
References:  23
Ovary, uterus, testis, prostate, brain, heart, intestine, colon, adrenal, thyroid, thymus, salivary gland, muscle, peripheral blood cells, bone marrow.
Species:  Human
Technique:  Multi-tissue expression array.
References:  6
Neuroendocrine/carcinoid tissues
Species:  Human
Technique:  Immunohistochemistry
References:  34
Bone marrow, spleen, blood, colon, haematopoietic stem cells, CD8+ T cells, B cells, CD40+ monocytes, dendritic, CD16+ NK cells, Th17, TFH, Treg cells
Species:  Human
Technique:  qPCR
References:  35
Skeletal muscle, heart, pancreas, ileum, colon
Species:  Mouse
Technique:  qPCR
References:  1
Bone marrow, lymph node, spleen, blood, colon, haematopoietic stem cells, CD8+ T cells, B cells, CD40+ monocytes, dendritic, CD16+ NK cells, CD4+ T cells
Species:  Mouse
Technique:  qPCR
References:  35
MIN6 (murine insulinoma) cells
Species:  Mouse
Technique:  qPCR
References:  3
Colon, caecum, nodose ganglion
Species:  Mouse
Technique:  RT-PCR
References:  11
Myenteric and submucosal plexus
Species:  Mouse
Technique:  In situ hybridisation
References:  11
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
GLP-1 release
Species:  Mouse
Tissue:  GLUTag cells
Response measured:  Increased secretion of GLP-1
References:  25
Measurement of cAMP levels in COS-7 cells transiently transfected with RXFP4 receptors. cAMP indicated by pCRE reporter gene.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  pCRE reporter gene inhibition
References:  22-24
Inhibition of pCRE reporter gene activation by forskolin
Species:  Mouse
Tissue:  HEK293 cells transiently expressing mouse RXFP4
Response measured:  Inhibition of pCRE reporter gene activation
References:  25
ERK1/2 activation
Species:  Human
Tissue:  HEK293 cells transiently expressing human RXFP4
Response measured:  Increased phosphorylation of ERK1/2
References:  25
ERK1/2 activation
Species:  Mouse
Tissue:  HEK293 cells transiently expressing mouse RXFP4
Response measured:  Increased phosphorylation of ERK1/2
References:  25
Inhibition of pCRE reporter gene activation by forskolin
Species:  Human
Tissue:  SK-N-MC cells transfected with pCRE reporter
Response measured:  Inhibition of pCRE reporter gene activation
References:  18
Inhibition of pCRE reporter gene activation by forskolin
Species:  Human
Tissue:  HEK293 cells transiently expressing human RXFP4
Response measured:  Inhibition of pCRE reporter gene activation
References:  25
Insulin secretion
Species:  Mouse
Tissue:  MIN6 insulinoma cells
Response measured:  Increased insulin secretion
References:  25
Inhibition of pCRE reporter gene activation by forskolin
Species:  Human
Tissue:  CHO cells stably or transiently expressing RXFP4
Response measured:  Inhibition of pCRE reporter gene activation
References:  4-5,15-16,18,20,23-24,31,39
GTPγS binding
Species:  Human
Tissue:  COS-7 cells transiently expressing RXFP4
Response measured:  Increased GTPγS binding
References:  18,23-24
cAMP accumulation
Species:  Human
Tissue:  NCI-H716 cells
Response measured:  Inhibition of forskolin-stimulated cAMP accumulation
References:  3
Insulin secretion
Species:  Mouse
Tissue:  MIN6 insulinoma cells
Response measured:  Inhibition of glucose stimulated insulin secretion
References:  3
pERK1/2 activation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Increased phosphorylation of ERK1/2
References:  2-4,20,27
S6RP activation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Increased phosphorylation of S6RP
References:  2-3
p38MAPK activation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Increased phosphorylation of p38MAPK
References:  2-3
Akt activation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Increased hosphorylation of Akt Ser473 and Thr308
References:  2-3
S6RP phosphorylation
Species:  Human
Tissue:  NCI-H716 enteroendocrine L cells
Response measured:  Increased phosphorylation of S6RP Ser235-236
References:  1
GTPγS binding
Species:  Human
Tissue:  CHO cells expressing RXFP4
Response measured:  Increased GTPγS binding
References:  9
pERK1/2 activation
Species:  Human
Tissue:  NCI-H716 enteroendocrine L cells
Response measured:  Increased phosphorylation of ERK1/2
References:  1
Akt phosphorylation
Species:  Human
Tissue:  NCI-H716 enteroendocrine L cells
Response measured:  Increased phosphorylation of Akt p-Ser473 and Akt p-Thr308
References:  1
Interaction between RXFP4 and GRK2, β-arrestins 1 & 2 and Rab5a
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Real time kinetic BRET of increased interaction between RXFP4 and GRK2, β-arrestin 1 & 2 or early endosome marker Rab5a
References:  2
Cell proliferation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Increased cell proliferation measured by BrdU uptake
References:  2
RXFP4 receptor binding
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Competition for binding of Eu-INSL5 at RXFP4
References:  4,21,27,29,32
Inhibition of cAMP accumulation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Inhibition of forskolin stimulated cAMP accumulation
References:  4,21,27,29,32,44
Real time inhibition of cAMP accumulation
Species:  Human
Tissue:  CHO cells stably expressing human RXFP4
Response measured:  Inhibition of forskolin stimulated cAMP accumulation using BRET based CAMYEL (cAMP sensor using YFP-Epac-Rluc)
References:  36
RXFP4 receptor binding
Species:  Human
Tissue:  HEK293 cells expressing human RXFP4
Response measured:  NanoBiT ligand receptor binding
References:  14,38
RXFP4 receptor binding
Species:  Human
Tissue:  CHO or HEK293 cells expressing human RXFP4
Response measured:  Competition for Eu labelled R3/I5 binding
References:  41-42,44
RXFP4 receptor binding
Species:  Human
Tissue:  HEK293 cells expressing human RXFP4
Response measured:  NanoLuc conjugated R3/I5 ligand receptor binding
References:  15-16,37,39-40,43
Physiological Functions Click here for help
Stimulation of food intake
Species:  Mouse
Tissue:  Orexigenic action in mouse
References:  11
Control of colonic contraction
Species:  Mouse
Tissue:  Orexigenic action in mouse
References:  11
Regulation of the immune system
Species:  Mouse
Tissue:  Widespread expression of Rxfp4 in all immune organs, moderately high in dendritic cells especially in spleen
References:  35
Control of colon motility
Species:  Mouse
Tissue:  Colon
References:  10,21
Physiological Consequences of Altering Gene Expression Click here for help
RXFP4 polymorphisms associated with higher BMI
Species:  Human
Tissue: 
Technique:  Single nucleotide polymorphism selection and genotyping
References:  26
RXFP4 knockout mice do not display orexigeneic action of INSL5
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  11
RXFP4 knockout mice lack the colonokinetic effect of INSL5
Species:  Mouse
Tissue:  Colon
Technique: 
References:  10
RXFP4 polymorphisms associated with mobilisation of haematopoietic stem cells
Species:  Human
Tissue:  Single nucleotide polymorphism selection and genotyping following G-CSF stimulation and isolation of CD34+ cells
Technique: 
References:  33

References

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1. Ang SY, Evans BA, Poole DP, Bron R, DiCello JJ, Bathgate RAD, Kocan M, Hutchinson DS, Summers RJ. (2018) INSL5 activates multiple signalling pathways and regulates GLP-1 secretion in NCI-H716 cells. J Mol Endocrinol, 60 (3): 213-224. [PMID:29535183]

2. Ang SY, Hutchinson DS, Evans BA, Hossain MA, Patil N, Bathgate RA, Kocan M, Summers RJ. (2017) The actions of relaxin family peptides on signal transduction pathways activated by the relaxin family peptide receptor RXFP4. Naunyn Schmiedebergs Arch Pharmacol, 390 (1): 105-111. [PMID:27888281]

3. Ang SY, Hutchinson DS, Patil N, Evans BA, Bathgate RAD, Halls ML, Hossain MA, Summers RJ, Kocan M. (2017) Signal transduction pathways activated by insulin-like peptide 5 at the relaxin family peptide RXFP4 receptor. Br J Pharmacol, 174 (10): 1077-1089. [PMID:27243554]

4. Belgi A, Bathgate RA, Kocan M, Patil N, Zhang S, Tregear GW, Wade JD, Hossain MA. (2013) Minimum active structure of insulin-like peptide 5. J Med Chem, 56 (23): 9509-16. [PMID:24188028]

5. Belgi A, Hossain MA, Shabanpoor F, Chan L, Zhang S, Bathgate RA, Tregear GW, Wade JD. (2011) Structure and function relationship of murine insulin-like peptide 5 (INSL5): free C-terminus is essential for RXFP4 receptor binding and activation. Biochemistry, 50 (39): 8352-61. [PMID:21866895]

6. Boels K, Schaller HC. (2003) Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor. Br J Pharmacol, 140 (5): 932-8. [PMID:14530218]

7. Chen J, Kuei C, Sutton SW, Bonaventure P, Nepomuceno D, Eriste E, Sillard R, Lovenberg TW, Liu C. (2005) Pharmacological characterization of relaxin-3/INSL7 receptors GPCR135 and GPCR142 from different mammalian species. J Pharmacol Exp Ther, 312 (1): 83-95. [PMID:15367576]

8. Chen Y, Zhou Q, Wang J, Xu Y, Wang Y, Yan J, Wang Y, Zhu Q, Zhao F, Li C et al.. (2023) Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4). Nat Commun, 14 (1): 492. [PMID:36717591]

9. DeChristopher B, Park SH, Vong L, Bamford D, Cho HH, Duvadie R, Fedolak A, Hogan C, Honda T, Pandey P et al.. (2019) Discovery of a small molecule RXFP3/4 agonist that increases food intake in rats upon acute central administration. Bioorg Med Chem Lett, 29 (8): 991-994. [PMID:30824200]

10. Diwakarla S, Bathgate RAD, Zhang X, Hossain MA, Furness JB. (2020) Colokinetic effect of an insulin-like peptide 5-related agonist of the RXFP4 receptor. Neurogastroenterol Motil, 32 (5): e13796. [PMID:31989750]

11. Grosse J, Heffron H, Burling K, Akhter Hossain M, Habib AM, Rogers GJ, Richards P, Larder R, Rimmington D, Adriaenssens AA et al.. (2014) Insulin-like peptide 5 is an orexigenic gastrointestinal hormone. Proc Natl Acad Sci USA, 111 (30): 11133-8. [PMID:25028498]

12. Guan D, Rahman MT, Gay EA, Vasukuttan V, Mathews KM, Decker AM, Williams AH, Zhan CG, Jin C. (2021) Indole-Containing Amidinohydrazones as Nonpeptide, Dual RXFP3/4 Agonists: Synthesis, Structure-Activity Relationship, and Molecular Modeling Studies. J Med Chem, 64 (24): 17866-17886. [PMID:34855388]

13. Haugaard-Kedström LM, Shabanpoor F, Hossain MA, Clark RJ, Ryan PJ, Craik DJ, Gundlach AL, Wade JD, Bathgate RA, Rosengren KJ. (2011) Design, synthesis, and characterization of a single-chain peptide antagonist for the relaxin-3 receptor RXFP3. J Am Chem Soc, 133 (13): 4965-74. [PMID:21384867]

14. Hu MJ, Shao XX, Li HZ, Nie WH, Wang JH, Liu YL, Xu ZG, Guo ZY. (2018) Development of a novel ligand binding assay for relaxin family peptide receptor 3 and 4 using NanoLuc complementation. Amino Acids, 50 (8): 1111-1119. [PMID:29770870]

15. Hu MJ, Shao XX, Wang JH, Wei D, Guo YQ, Liu YL, Xu ZG, Guo ZY. (2016) Mechanism for insulin-like peptide 5 distinguishing the homologous relaxin family peptide receptor 3 and 4. Sci Rep, 6: 29648. [PMID:27404393]

16. Hu MJ, Wei D, Shao XX, Wang JH, Liu YL, Xu ZG, Guo ZY. (2017) Interaction mechanism of insulin-like peptide 5 with relaxin family peptide receptor 4. Arch Biochem Biophys, 619: 27-34. [PMID:28274616]

17. Khalaf MS, Coles MP, Hitchcock PB. (2008) A structural, theoretical and coordinative evaluation of the bicyclic guanidinate derived from 1,4,6-triazabicyclo[3.3.0]oct-4-ene. Dalton Trans, (32): 4288-95. [PMID:18682868]

18. Kuei C, Sutton S, Bonaventure P, Pudiak C, Shelton J, Zhu J, Nepomuceno D, Wu J, Chen J, Kamme F et al.. (2007) R3(BDelta23 27)R/I5 chimeric peptide, a selective antagonist for GPCR135 and GPCR142 over relaxin receptor LGR7: in vitro and in vivo characterization. J Biol Chem, 282 (35): 25425-35. [PMID:17606621]

19. Lin G, Feng Y, Cai X, Zhou C, Shao L, Chen Y, Chen L, Liu Q, Zhou Q, Bathgate RAD et al.. (2021) High-Throughput Screening Campaign Identified a Potential Small Molecule RXFP3/4 Agonist. Molecules, 26 (24): 7511. [PMID:34946593]

20. Lin GY, Lin L, Cai XQ, Dai AT, Zhu Y, Li J, Liu Q, Yang DH, Bathgate RAD, Wang MW. (2020) High-throughput screening campaign identifies a small molecule agonist of the relaxin family peptide receptor 4. Acta Pharmacol Sin, 41 (10): 1328-1336. [PMID:32235863]

21. Lin L, Lin G, Zhou Q, Bathgate RAD, Gong GQ, Yang D, Liu Q, Wang MW. (2021) Design, synthesis and pharmacological evaluation of tricyclic derivatives as selective RXFP4 agonists. Bioorg Chem, 110: 104782. [PMID:33730669]

22. Liu C, Chen J, Kuei C, Sutton S, Nepomuceno D, Bonaventure P, Lovenberg TW. (2005) Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7. Mol Pharmacol, 67 (1): 231-40. [PMID:15465925]

23. Liu C, Chen J, Sutton S, Roland B, Kuei C, Farmer N, Sillard R, Lovenberg TW. (2003) Identification of relaxin-3/INSL7 as a ligand for GPCR142. J Biol Chem, 278 (50): 50765-70. [PMID:14522967]

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