Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [4,16]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1 (RLN1, P04808), relaxin (RLN2, P04090), relaxin-3 (RLN3, Q8WXF3) (also known as INSL7), insulin-like peptide 3 (INSL3 (INSL3, P51460)) and INSL5 (INSL5, Q9Y5Q6). Species homologues of relaxin have distinct pharmacology and relaxin (RLN2, P04090) interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [45]. Relaxin-3 (RLN3, Q8WXF3) is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [44]. INSL5 (INSL5, Q9Y5Q6) is the ligand for RXFP4 but is a weak antagonist of RXFP3. Relaxin (RLN2, P04090) and INSL3 (INSL3, P51460) have multiple complex binding interactions with RXFP1 [48] and RXFP2 [21] which direct the N-terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct receptor signaling [46]. INSL5 (INSL5, Q9Y5Q6) and relaxin-3 (RLN3, Q8WXF3) interact with their receptors using distinct residues in their B-chains for binding, and activation, respectively [28,60].

Relaxin (RLN2, P04090) is the cognate peptide ligand for RXFP1 and is in extended Phase III clinical trials for the treatment of acute heart failure [39]. Relaxin has vasodilatory, anti-fibrotic, angiogenic, anti-apoptotic and anti-inflammatory effects. A small molecule allosteric agonists ML290 has been developed [54,62], and a relaxin B-chain mimetic peptide B7-33 has been developed which that has cell specific signaling properties [23]. The antifibrotic actions of relaxin are dependent on the angiotensin receptor AT₂ [7]. INSL3 (INSL3, P51460) is the cognate peptide for RXFP2 and is a circulating hormone that in males is essential for testicular descent in utero [41] and in females has important roles in ovarian follicle function [29]. In adults, INSL3 has potential roles in testicular function [30] and the musculo-skeletal system [8]. RXFP2 is also present in brain, associated with cortico-thalamic motor circuits [47]. cAMP elevation is the major signalling pathway for both RXFP1 and RXFP2 [26-27], but RXFP1 also activates MAP kinases, nitric oxide signalling, and tyrosine kinase phosphorylation; and relaxin can interact with glucocorticoid receptors [18]. Receptor expression profiles suggest that RXFP3 is a brain neuropeptide receptor and RXFP4 a gut hormone receptor. The brain relaxin-3/RXFP3 system modulates feeding [11-12,20,49,55] via effects in hypothalamus [9,11,31], anxiety [43,63], reward and motivated, goal-directed behaviours [22,43,59], and spatial and social memory [1,14]. Of the other relaxin peptides, relaxin-3 (RLN3, Q8WXF3) is an agonist at RXFP3 and RXFP4 whereas INSL5 (INSL5, Q9Y5Q6) is an agonist at RXFP4 and a weak antagonist at RXFP3. INSL5 (INSL5, Q9Y5Q6) is secreted from enteroendocrine L cells and the INSL5/RXFP4 system affects food intake [13] and glucose homeostasis [37]. RXFP3 and RXFP4 couple to G_i/o and inhibit adenylyl cyclase [36,57], and also cause Erk1/2 phosphorylation [57]. RXFP4 also causes phosphorylation of p38MAPK, Akt and S6RP [3] and GLP-1 secretion in vitro [2]. There is evidence that at RXFP3, relaxin (RLN2, P04090) is a biased ligand compared to the cognate ligand relaxin-3 (RLN3, Q8WXF3) [57].

* Key recommended reading is highlighted with an asterisk

* Bathgate RA, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ. (2013) Relaxin family peptides and their receptors. Physiol. Rev., 93 (1): 405-80. [PMID:23303914]

Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ. (2006) International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. Pharmacol Rev, 58: 7-31. [PMID:16507880]

Callander GE, Bathgate RA. (2010) Relaxin family peptide systems and the central nervous system. Cell. Mol. Life Sci., 67 (14): 2327-41. [PMID:20213277]

* Du XJ, Bathgate RA, Samuel CS, Dart AM, Summers RJ. (2010) Cardiovascular effects of relaxin: from basic science to clinical therapy. Nat Rev Cardiol, 7 (1): 48-58. [PMID:19935741]

* Halls ML, Bathgate RA, Sutton SW, Dschietzig TB, Summers RJ. (2015) International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides. Pharmacol. Rev., 67 (2): 389-440. [PMID:25761609]

* Ivell R, Kotula-Balak M, Glynn D, Heng K, Anand-Ivell R. (2011) Relaxin family peptides in the male reproductive system--a critical appraisal. Mol. Hum. Reprod., 17 (2): 71-84. [PMID:20952422]

Kong RC, Shilling PJ, Lobb DK, Gooley PR, Bathgate RA. (2010) Membrane receptors: structure and function of the relaxin family peptide receptors. Mol. Cell. Endocrinol., 320 (1-2): 1-15. [PMID:20138959]

van der Westhuizen ET, Halls ML, Samuel CS, Bathgate RA, Unemori EN, Sutton SW, Summers RJ. (2008) Relaxin family peptide receptors--from orphans to therapeutic targets. Drug Discov. Today, 13 (15-16): 640-51. [PMID:18675759]

1. Albert-Gasco H, Sanchez-Sarasua S, Ma S, García-Díaz C, Gundlach AL, Sanchez-Perez AM, Olucha-Bordonau FE. (2019) Central relaxin-3 receptor (RXFP3) activation impairs social recognition and modulates ERK-phosphorylation in specific GABAergic amygdala neurons. Brain Struct Funct, 224 (1): 453-469. [PMID:30368554]

2. 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]

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. Bathgate RA, Ivell R, Sanborn BM, Sherwood OD, Summers RJ. (2006) International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. Pharmacol Rev, 58: 7-31. [PMID:16507880]

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. Büllesbach EE, Schwabe C. (2005) LGR8 signal activation by the relaxin-like factor. J Biol Chem, 280: 14586-14590. [PMID:15708846]

7. Chow BS, Kocan M, Bosnyak S, Sarwar M, Wigg B, Jones ES, Widdop RE, Summers RJ, Bathgate RA, Hewitson TD et al.. (2014) Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis. Kidney Int., 86 (1): 75-85. [PMID:24429402]

8. De Toni L, Agoulnik AI, Sandri M, Foresta C, Ferlin A. (2019) INSL3 in the muscolo-skeletal system. Mol. Cell. Endocrinol., [Epub ahead of print]. [PMID:30625346]

9. de Ávila C, Chometton S, Lenglos C, Calvez J, Gundlach AL, Timofeeva E. (2018) Differential effects of relaxin-3 and a selective relaxin-3 receptor agonist on food and water intake and hypothalamic neuronal activity in rats. Behav. Brain Res., 336: 135-144. [PMID:28864207]

10. Del Borgo MP, Hughes RA, Bathgate RA, Lin F, Kawamura K, Wade JD. (2006) Analogs of insulin-like peptide 3 (INSL3) B-chain are LGR8 antagonists in vitro and in vivo. J Biol Chem,: 727-729. [PMID:16547350]

11. Ganella DE, Callander GE, Ma S, Bye CR, Gundlach AL, Bathgate RA. (2013) Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus. Gene Ther., 20 (7): 703-16. [PMID:23135160]

12. Ganella DE, Ryan PJ, Bathgate RA, Gundlach AL. (2012) Increased feeding and body weight gain in rats after acute and chronic activation of RXFP3 by relaxin-3 and receptor-selective peptides: functional and therapeutic implications. Behav Pharmacol, 23 (5-6): 516-25. [PMID:22854307]

13. 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. U.S.A., 111 (30): 11133-8. [PMID:25028498]

14. Haidar M, Guèvremont G, Zhang C, Bathgate RAD, Timofeeva E, Smith CM, Gundlach AL. (2017) Relaxin-3 inputs target hippocampal interneurons and deletion of hilar relaxin-3 receptors in "floxed-RXFP3" mice impairs spatial memory. Hippocampus, 27 (5): 529-546. [PMID:28100033]

15. Halls ML, Bathgate RA, Summers RJ. (2006) Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by distinct mechanisms. Mol. Pharmacol., 70 (1): 214-26. [PMID:16569707]

16. Halls ML, Bathgate RA, Sutton SW, Dschietzig TB, Summers RJ. (2015) International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides. Pharmacol. Rev., 67 (2): 389-440. [PMID:25761609]

17. Halls ML, Bond CP, Sudo S, Kumagai J, Ferraro T, Layfield S, Bathgate RA, Summers RJ. (2005) Multiple binding sites revealed by interaction of relaxin family peptides with native and chimeric relaxin family peptide receptors 1 and 2 (LGR7 and LGR8). J Pharmacol Exp Ther, 313: 677-687. [PMID:15649866]

18. Halls ML, van der Westhuizen ET, Bathgate RA, Summers RJ. (2007) Relaxin family peptide receptors--former orphans reunite with their parent ligands to activate multiple signalling pathways. Br. J. Pharmacol., 150 (6): 677-91. [PMID:17293890]

19. Halls ML, van der Westhuizen ET, Wade JD, Evans BA, Bathgate RA, Summers RJ. (2009) Relaxin family peptide receptor (RXFP1) coupling to G(alpha)i3 involves the C-terminal Arg752 and localization within membrane Raft Microdomains. Mol. Pharmacol., 75 (2): 415-28. [PMID:19029286]

20. 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]

21. Hoare BL, Bruell S, Sethi A, Gooley PR, Lew MJ, Hossain MA, Inoue A, Scott DJ, Bathgate RAD. (2019) Multi-Component Mechanism of H2 Relaxin Binding to RXFP1 through NanoBRET Kinetic Analysis. iScience, 11: 93-113. [PMID:30594862]

22. Hosken IT, Sutton SW, Smith CM, Gundlach AL. (2015) Relaxin-3 receptor (Rxfp3) gene knockout mice display reduced running wheel activity: Implications for role of relaxin-3/RXFP3 signalling in sustained arousal. Behav. Brain Res., 278: 167-75. [PMID:25257104]

23. Hossain MA, Kocan M, Yao ST, Royce SG, Nair VB, Siwek C, Patil NA, Harrison IP, Rosengren KJ, Selemidis S et al.. (2016) A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1. Chem Sci, 7 (6): 3805-3819. [PMID:30155023]

24. Hossain MA, Rosengren KJ, Haugaard-Jönsson LM, Zhang S, Layfield S, Ferraro T, Daly NL, Tregear GW, Wade JD, Bathgate RA. (2008) The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors. J. Biol. Chem., 283 (25): 17287-97. [PMID:18434306]

25. Hossain MA, Samuel CS, Binder C, Hewitson TD, Tregear GW, Wade JD, Bathgate RA. (2010) The chemically synthesized human relaxin-2 analog, B-R13/17K H2, is an RXFP1 antagonist. Amino Acids, 39 (2): 409-16. [PMID:20043231]

26. Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ. (2000) The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Mol Endocrinol, 14: 1257-1271. [PMID:10935549]

27. Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ. (2002) Activation of orphan receptors by the hormone relaxin. Science, 295: 671-674. [PMID:11809971]

28. 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]

29. Ivell R, Anand-Ivell R. (2018) Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive physiology. Hum. Reprod. Update, 24 (6): 639-651. [PMID:30204868]

30. Ivell R, Kotula-Balak M, Glynn D, Heng K, Anand-Ivell R. (2011) Relaxin family peptides in the male reproductive system--a critical appraisal. Mol. Hum. Reprod., 17 (2): 71-84. [PMID:20952422]

31. Kania A, Gugula A, Grabowiecka A, de Ávila C, Blasiak T, Rajfur Z, Lewandowski MH, Hess G, Timofeeva E, Gundlach AL et al.. (2017) Inhibition of oxytocin and vasopressin neuron activity in rat hypothalamic paraventricular nucleus by relaxin-3-RXFP3 signalling. J. Physiol. (Lond.), 595 (11): 3425-3447. [PMID:28098344]

32. 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]

33. Kumagai J, Hsu SY, Matsumi H, Roh JS, Fu P, Wade JD, Bathgate RA, Hsueh AJ. (2002) INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J Biol Chem, 277: 31283-31286. [PMID:12114498]

34. 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: 231-240. [PMID:15465925]

35. 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: 50765-50770. [PMID:14522967]

36. Liu C, Eriste E, Sutton S, Chen J, Roland B, Kuei C, Farmer N, Jörnvall H, Sillard R, Lovenberg TW. (2003) Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135. J Biol Chem, 278: 50754-50764. [PMID:14522968]

37. Luo X, Li T, Zhu Y, Dai Y, Zhao J, Guo ZY, Wang MW. (2015) The insulinotrophic effect of insulin-like peptide 5 in vitro and in vivo. Biochem. J., 466 (3): 467-73. [PMID:25514935]

38. Matsumoto M, Kamohara M, Sugimoto T, Hidaka K, Takasaki J, Saito T, Okada M, Yamaguchi T, Furuichi K. (2000) The novel G-protein coupled receptor SALPR shares sequence similarity with somatostatin and angiotensin receptors. Gene, 248: 183-189. [PMID:10806363]

39. Metra M, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, Ponikowski P, Unemori E, Voors AA, Adams Jr KF et al.. (2013) Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes. J. Am. Coll. Cardiol., 61 (2): 196-206. [PMID:23273292]

40. Muda M, He C, Martini PG, Ferraro T, Layfield S, Taylor D, Chevrier C, Schweickhardt R, Kelton C, Ryan PL, Bathgate RA. (2005) Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity. Mol Hum Reprod, 11: 591-600. [PMID:16051677]

41. Nef S, Parada LF. (1999) Cryptorchidism in mice mutant for Insl3. Nat. Genet., 22 (3): 295-9. [PMID:10391220]

42. Neschadim A, Pritzker LB, Pritzker KP, Branch DR, Summerlee AJ, Trachtenberg J, Silvertown JD. (2014) Relaxin receptor antagonist AT-001 synergizes with docetaxel in androgen-independent prostate xenografts. Endocr. Relat. Cancer, 21 (3): 459-71. [PMID:24812057]

43. Ryan PJ, Kastman HE, Krstew EV, Rosengren KJ, Hossain MA, Churilov L, Wade JD, Gundlach AL, Lawrence AJ. (2013) Relaxin-3/RXFP3 system regulates alcohol-seeking. Proc. Natl. Acad. Sci. U.S.A., 110 (51): 20789-94. [PMID:24297931]

44. Scott DJ, Fu P, Shen PJ, Gundlach A, Layfield S, Riesewijk A, Tomiyama H, Hutson JM, Tregear GW, Bathgate RA. (2005) Characterization of the rat INSL3 receptor. Ann N Y Acad Sci, 1041: 13-16. [PMID:15956681]

45. Scott DJ, Layfield S, Riesewijk A, Morita H, Tregear GW, Bathgate RA. (2005) Characterization of the mouse and rat relaxin receptors. Ann. N. Y. Acad. Sci., 1041: 8-12. [PMID:15956680]

46. Scott DJ, Layfield S, Yan Y, Sudo S, Hsueh AJ, Tregear GW, Bathgate RA. (2006) Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor signaling is mediated by their unique low density lipoprotein class A modules. J. Biol. Chem., 281 (46): 34942-54. [PMID:16963451]

47. Sedaghat K, Shen PJ, Finkelstein DI, Henderson JM, Gundlach AL. (2008) Leucine-rich repeat-containing G-protein-coupled receptor 8 in the rat brain: Enrichment in thalamic neurons and their efferent projections. Neuroscience, 156 (2): 319-33. [PMID:18706979]

48. Sethi A, Bruell S, Patil N, Hossain MA, Scott DJ, Petrie EJ, Bathgate RA, Gooley PR. (2016) The complex binding mode of the peptide hormone H2 relaxin to its receptor RXFP1. Nat Commun, 7: 11344. [PMID:27088579]

49. Shabanpoor F, Akhter Hossain M, Ryan PJ, Belgi A, Layfield S, Kocan M, Zhang S, Samuel CS, Gundlach AL, Bathgate RA et al.. (2012) Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1. J. Med. Chem., 55 (4): 1671-81. [PMID:22257012]

50. Shabanpoor F, Bathgate RA, Belgi A, Chan LJ, Nair VB, Wade JD, Hossain MA. (2012) Site-specific conjugation of a lanthanide chelator and its effects on the chemical synthesis and receptor binding affinity of human relaxin-2 hormone. Biochem. Biophys. Res. Commun., 420 (2): 253-6. [PMID:22425984]

51. Shabanpoor F, Bathgate RA, Hossain MA, Giannakis E, Wade JD, Hughes RA. (2007) Design, synthesis and pharmacological evaluation of cyclic mimetics of the insulin-like peptide 3 (INSL3) B-chain. J. Pept. Sci., 13 (2): 113-20. [PMID:17120268]

52. Shabanpoor F, Hughes RA, Bathgate RA, Zhang S, Scanlon DB, Lin F, Hossain MA, Separovic F, Wade JD. (2008) Solid-phase synthesis of europium-labeled human INSL3 as a novel probe for the study of ligand-receptor interactions. Bioconjug. Chem., 19 (7): 1456-63. [PMID:18529069]

53. Shabanpoor F, Zhang S, Hughes RA, Hossain MA, Layfield S, Ferraro T, Bathgate RA, Separovic F, Wade JD. (2011) Design and development of analogues of dimers of insulin-like peptide 3 B-chain as high-affinity antagonists of the RXFP2 receptor. Biopolymers, 96 (1): 81-7. [PMID:20560146]

54. Shemesh R, Toporik A, Levine Z, Hecht I, Rotman G, Wool A, Dahary D, Gofer E, Kliger Y, Soffer MA et al.. (2008) Discovery and validation of novel peptide agonists for G-protein-coupled receptors. J. Biol. Chem., 283 (50): 34643-9. [PMID:18854305]

55. Smith CM, Hosken IT, Sutton SW, Lawrence AJ, Gundlach AL. (2012) Relaxin-3 null mutation mice display a circadian hypoactivity phenotype. Genes Brain Behav., 11 (1): 94-104. [PMID:21899720]

56. Sudo S, Kumagai J, Nishi S, Layfield S, Ferraro T, Bathgate RA, Hsueh AJ. (2003) H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2. J Biol Chem, 278: 7855-7862. [PMID:12506116]

57. van der Westhuizen ET, Christopoulos A, Sexton PM, Wade JD, Summers RJ. (2010) H2 relaxin is a biased ligand relative to H3 relaxin at the relaxin family peptide receptor 3 (RXFP3). Mol. Pharmacol., 77 (5): 759-72. [PMID:20159943]

58. Van Der Westhuizen ET, Summers RJ, Halls ML, Bathgate RA, Sexton PM. (2007) Relaxin receptors--new drug targets for multiple disease states. Curr Drug Targets, 8 (1): 91-104. [PMID:17266534]

59. Walker AW, Smith CM, Chua BE, Krstew EV, Zhang C, Gundlach AL, Lawrence AJ. (2015) Relaxin-3 receptor (RXFP3) signalling mediates stress-related alcohol preference in mice. PLoS ONE, 10 (4): e0122504. [PMID:25849482]

60. Wong LLL, Scott DJ, Hossain MA, Kaas Q, Rosengren KJ, Bathgate RAD. (2018) Distinct but overlapping binding sites of agonist and antagonist at the relaxin family peptide 3 (RXFP3) receptor. J. Biol. Chem., 293 (41): 15777-15789. [PMID:30131340]

61. Xiao J, Chen CZ, Huang Z, Agoulnik IU, Ferrer M, Southall N, Hu X, Zheng W, Agoulnik AI, Marugan JJ. (2010) Discovery, optimization, and biological activity of the first potent and selective small-molecule agonist series of human relaxin receptor 1 (RXFP1). Probe Reports from the NIH Molecular Libraries Program,. [PMID:23905199]

62. Xiao J, Huang Z, Chen CZ, Agoulnik IU, Southall N, Hu X, Jones RE, Ferrer M, Zheng W, Agoulnik AI et al.. (2013) Identification and optimization of small-molecule agonists of the human relaxin hormone receptor RXFP1. Nat Commun, 4: 1953. [PMID:23764525]

63. Zhang C, Chua BE, Yang A, Shabanpoor F, Hossain MA, Wade JD, Rosengren KJ, Smith CM, Gundlach AL. (2015) Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice. Behav. Brain Res., 292: 125-32. [PMID:26057358]

64. Zhang S, Hughes RA, Bathgate RA, Shabanpoor F, Hossain MA, Lin F, van Lierop B, Robinson AJ, Wade JD. (2010) Role of the intra-A-chain disulfide bond of insulin-like peptide 3 in binding and activation of its receptor, RXFP2. Peptides, 31 (9): 1730-6. [PMID:20570702]

65. Zhu J, Kuei C, Sutton S, Kamme F, Yu J, Bonaventure P, Atack J, Lovenberg TW, Liu C. (2008) Identification of the domains in RXFP4 (GPCR142) responsible for the high affinity binding and agonistic activity of INSL5 at RXFP4 compared to RXFP3 (GPCR135). Eur. J. Pharmacol., 590 (1-3): 43-52. [PMID:18582868]

Subcommittee members: Roger Summers (Chairperson) Drug Discovery Biology Monash Institute of Pharmaceutical Sciences Monash University 399 Royal Parade Parkville,Victoria 3052 AUSTRALIA Michelle Halls Drug Discovery Biology Monash Institute of Pharmaceutical Sciences Monash University 399 Royal Parade Parkville, Victoria 3052 AUSTRALIA Ross Bathgate Florey Institute of Neuroscience and Mental Health University of Melbourne Victoria 3010 AUSTRALIA Thomas Dschietzig Immundiagnostik AG Bensheim, Germany Charité-University Medicine Berlin Campus Mitte Medical Clinic for Cardiology and Angiology Berlin, Germany Relaxera Pharmazeutische Gesellschaft mbH & Co. KG, Bensheim, Germany Andrew L. Gundlach Florey Institute of Neuroscience and Mental Health The University of Melbourne Victoria 3010 Australia