RXFP3

Summary

RXFP3 (relaxin family peptide receptor 3, HGNC:24883) is a protein-coding gene on chromosome 5p13.2, encoding Relaxin-3 receptor 1 (Q9NSD7). Receptor for RNL3/relaxin-3.

Predicted to enable G protein-coupled peptide receptor activity. Involved in positive regulation of cytokinesis. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 51289 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_016568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24883
Approved symbol	RXFP3
Name	relaxin family peptide receptor 3
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	SALPR, GPCR135, RXFPR3
Ensembl gene	ENSG00000182631
Ensembl biotype	protein_coding
OMIM	609445
Entrez	51289

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000330120

RefSeq mRNA: 1 — MANE Select: NM_016568 NM_016568

CCDS: CCDS3900

Canonical transcript exons

ENST00000330120 — 1 exons

Exon	Start	End
ENSE00001294458	33936386	33938918

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 63.84.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	63.84	gold quality
islet of Langerhans	UBERON:0000006	58.26	gold quality
right adrenal gland cortex	UBERON:0035827	50.15	gold quality
left adrenal gland cortex	UBERON:0035825	47.54	gold quality
right adrenal gland	UBERON:0001233	46.02	gold quality
adrenal gland	UBERON:0002369	45.17	gold quality
prefrontal cortex	UBERON:0000451	43.29	gold quality
left adrenal gland	UBERON:0001234	42.60	gold quality
superior frontal gyrus	UBERON:0002661	41.86	silver quality
colonic epithelium	UBERON:0000397	41.14	gold quality
cortical plate	UBERON:0005343	39.99	gold quality
pancreas	UBERON:0001264	39.11	gold quality
primary visual cortex	UBERON:0002436	39.04	gold quality
bone marrow cell	CL:0002092	38.57	gold quality
adenohypophysis	UBERON:0002196	38.55	gold quality
hypothalamus	UBERON:0001898	38.41	gold quality
ganglionic eminence	UBERON:0004023	37.38	gold quality
frontal cortex	UBERON:0001870	36.92	gold quality
placenta	UBERON:0001987	36.66	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
sural nerve	UBERON:0015488	36.42	gold quality
pituitary gland	UBERON:0000007	36.32	gold quality
apex of heart	UBERON:0002098	35.01	gold quality
skeletal muscle tissue	UBERON:0001134	34.70	gold quality
granulocyte	CL:0000094	34.53	gold quality
bone marrow	UBERON:0002371	34.08	gold quality
caudate nucleus	UBERON:0001873	32.76	silver quality
cerebral cortex	UBERON:0000956	32.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
vermiform appendix	UBERON:0001154	32.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting RXFP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-6853-5P	93.94	61.88	114

Literature-anchored findings (GeneRIF, showing 19)

• GPCR135 (SALPR) is the receptor for relaxin-3 (PMID:14522968)
• Substitution of the relaxin-3 A-chain with the A-chain from insulin-like peptide 5 results in a chimeric peptide that selectively activates GPCR135 and GPCR142. (PMID:15465925)
• functional response to H3 relaxin and other relaxin/insulin peptides of GPCR135 expressed in CHO-K1 cells was measured in the cytosensor microphysiometer and analyzed using inhibitors of signal transduction proteins (PMID:15956730)
• analysis of truncated human relaxin-2 and -3 (H2 and H3) relaxin peptides and their binding and cAMP activities on RXFP1, RXFP2, and RXFP3 (PMID:18434306)
• the N-terminus and EL2 domains of RXFP3 and RXFP4 are involved in ligand binding while TM2, 3, and 5 are critical for receptor activation. (PMID:18582868)
• Results decribe the structural and functional aspects of the interaction between relaxin-3 and its receptor, RXFP3. (PMID:19152634)
• H3 relaxin potently activates all signaling pathways coupled to RXFP3, whereas H2 relaxin is an AP-1-biased ligand relative to H3 relaxin. (PMID:20159943)
• Methylation status of CIDEA, HAAO and RXFP3 had significant association with microsatellite instability in endometrial tumors. (PMID:20211485)
• demonstrate the existence of an allosteric site for modulation of RXFP3 (PMID:22347403)
• Glu141 and Asp145 of the RXFP3 interact with the highly conserved arginine residues of relaxin-3. (PMID:24615237)
• we demonstrated distinct patterns of signalling for H3 and H2 relaxin and R3(BDelta23-27)R/I5 at the RXFP3 receptor (PMID:24641548)
• the negatively charged transmembrane aspartate residue controls activation of the relaxin-3 receptor RXFP3 (PMID:27353281)
• The role of these four INSL5 determinants in distinguishing RXFP4 from RXFP3. (PMID:27404393)
• Therefore, we conclude that stapling of the relaxin3 B chain does not compromise its ability to activate RXFP3 and is a promising method for developing stable peptide agonists and antagonists of RXFP3 to aid relaxin-3/RXFP3 research. (PMID:27498038)
• This study indicated that RXFP3 mainly localised in the post-acrosomal region of sperm head and neck. (PMID:29159832)
• present work shed new light on the interaction mechanism of RXFP3 and RXFP4 with agonists and antagonists, and also provided a novel approach for interaction studies of some plasma membrane receptors with their ligands. (PMID:30684458)
• Hydrophobic interactions of relaxin family peptide receptor 3 with ligands identified using a NanoBiT-based binding assay. (PMID:32810565)
• The putative role of the relaxin-3/RXFP3 system in clinical depression and anxiety: A systematic literature review. (PMID:34537263)
• Investigating the role of the relaxin-3/RXFP3 system in neuropsychiatric disorders and metabolic phenotypes: A candidate gene approach. (PMID:37967073)

Cross-species orthologs

0 orthologs

Paralogs (7): GPR174 (ENSG00000147138), GPR146 (ENSG00000164849), GPR183 (ENSG00000169508), GPR151 (ENSG00000173250), GPR132 (ENSG00000183484), GPR141 (ENSG00000187037), P2RY11 (ENSG00000244165)

Protein

Protein identifiers

Relaxin-3 receptor 1 — Q9NSD7 (reviewed: Q9NSD7)

Alternative names: G protein-coupled receptor SALPR, G-protein coupled receptor GPCR135, Relaxin family peptide receptor 3, Somatostatin- and angiotensin-like peptide receptor

All UniProt accessions (1): Q9NSD7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for RNL3/relaxin-3. Binding of the ligand inhibit cAMP accumulation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly in brain regions. Highest expression in substantia nigra and pituitary, followed by hippocampus, spinal cord, amygdala, caudate nucleus and corpus callosum, quite low level in cerebellum. In peripheral tissues, relatively high levels in adrenal glands, low levels in pancreas, salivary gland, placenta, mammary gland and testis.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_057652* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (19 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9KFI	ELECTRON MICROSCOPY	2.91
9KFJ	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSD7-F1	74.18	0.47

Antibody-complex structures (SAbDab): 2 — 9KFI, 9KFJ

Functional residue map

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

Disulfide bonds (1): 155–247

Glycosylation sites (2): 36, 40

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-444821	Relaxin receptors

MSigDB gene sets: 42 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, NRSF_01, GOBP_CELL_DIVISION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE, GOBP_CELL_CYCLE_PROCESS

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), positive regulation of cytokinesis (GO:0032467), signal transduction (GO:0007165)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), galanin receptor activity (GO:0004966)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Peptide ligand-binding receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor activity	1
signal transduction	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
neuropeptide receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RXFP3	RLN3	Q8WXF3	999
RXFP3	RXFP1	Q9HBX9	897
RXFP3	RLN1	P04808	882
RXFP3	INSL5	Q9Y5Q6	868
RXFP3	RLN2	P04090	865
RXFP3	RXFP2	Q8WXD0	835
RXFP3	INSL3	P51460	763
RXFP3	INS	P01308	663
RXFP3	INSL6	Q9Y581	662
RXFP3	ZNF671	Q8TAW3	607
RXFP3	INSL4	Q14641	596
RXFP3	SST	P01166	570
RXFP3	GIT2	Q14161	560
RXFP3	DRD4	P21917	507
RXFP3	ASTN1	O14525	506

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TMEM248	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
ENO1	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
GNAS	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
HSP90B1	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
KATNB1	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
NCKIPSD	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
TTC19	RXFP3	psi-mi:“MI:0915”(physical association)	0.370
YWHAE	RXFP3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (11): TMEM248 (Two-hybrid), ENO1 (Two-hybrid), GNAS (Two-hybrid), HSP90B1 (Two-hybrid), KATNB1 (Two-hybrid), NCKIPSD (Two-hybrid), TTC19 (Two-hybrid), YWHAE (Two-hybrid), RLN3 (Reconstituted Complex), RLN3 (Protein-peptide), APP (Reconstituted Complex)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B4XF06, D4A3U0, O43194, O55040, O88319, O95136, P0C0W8, P11617, P20272, P20789, P21554, P29274, P30543, P32940, P34972, P34979, P46616, P47746, P47752, P47936, P49684, P50129, P51810, P52592, P70259, Q58CW4, Q5IS73, Q5U431, Q60613, Q6DWJ6, Q6TLI7, Q71SP5, Q75Z89, Q7TQN9, Q80UC8, Q8BGE9, Q8BZ39, Q8BZL4

Diamond homologs: A0T2N3, F1MV99, O00155, O00590, O08707, O08858, O09027, O35210, O77590, O88410, O89039, O97666, P0C5I1, P0C7U4, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30680, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32303, P32745, P33396, P33535, P34976, P34993

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

36 predictions. Top by Δscore:

Variant	Effect	Δscore
5:33936588:G:GT	donor_gain	0.7600
5:33936600:ACCC:A	donor_gain	0.6800
5:33936594:C:G	donor_gain	0.5500
5:33936433:G:T	donor_gain	0.4500
5:33936433:G:GT	donor_gain	0.4200
5:33936454:GACC:G	donor_gain	0.3800
5:33936624:A:AG	donor_gain	0.3700
5:33936625:G:GG	donor_gain	0.3700
5:33937755:T:A	acceptor_gain	0.3600
5:33936569:G:GT	donor_gain	0.3200
5:33937823:G:GT	donor_gain	0.3200
5:33937837:GCCAG:G	donor_loss	0.3000
5:33937838:CCAG:C	donor_loss	0.3000
5:33937839:CAG:C	donor_loss	0.3000
5:33937840:AGGTA:A	donor_loss	0.3000
5:33937841:GG:G	donor_loss	0.3000
5:33937842:G:A	donor_loss	0.3000
5:33937843:T:A	donor_loss	0.3000
5:33937750:T:A	acceptor_gain	0.2900
5:33937824:G:GT	donor_loss	0.2800
5:33937836:TGCCA:T	donor_loss	0.2800
5:33936597:A:AG	donor_gain	0.2700
5:33936598:G:GG	donor_gain	0.2700
5:33937752:T:TA	acceptor_gain	0.2700
5:33937844:A:G	donor_loss	0.2600
5:33937769:GGC:G	acceptor_gain	0.2500
5:33937609:T:A	acceptor_gain	0.2400
5:33937825:A:AG	donor_gain	0.2400
5:33937826:G:GG	donor_gain	0.2400
5:33936546:C:G	donor_gain	0.2300

AlphaMissense

3025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:33937860:A:C	S374R	0.996
5:33937862:C:A	S374R	0.996
5:33937862:C:G	S374R	0.996
5:33937184:G:C	W148C	0.994
5:33937184:G:T	W148C	0.994
5:33937182:T:A	W148R	0.993
5:33937182:T:C	W148R	0.993
5:33937762:C:A	P341H	0.990
5:33937762:C:G	P341R	0.990
5:33937866:T:C	C376R	0.990
5:33937269:A:C	S177R	0.987
5:33937271:T:A	S177R	0.987
5:33937271:T:G	S177R	0.987
5:33937203:T:A	C155S	0.986
5:33937204:G:C	C155S	0.986
5:33937566:T:C	F276L	0.986
5:33937568:C:A	F276L	0.986
5:33937568:C:G	F276L	0.986
5:33937743:T:C	F335L	0.984
5:33937745:C:A	F335L	0.984
5:33937745:C:G	F335L	0.984
5:33937192:G:T	G151V	0.982
5:33937147:C:G	P136R	0.980
5:33936993:A:C	S85R	0.979
5:33936995:C:A	S85R	0.979
5:33936995:C:G	S85R	0.979
5:33937884:A:C	S382R	0.979
5:33937886:C:A	S382R	0.979
5:33937886:C:G	S382R	0.979
5:33937147:C:A	P136H	0.978

dbSNP variants (sampled 300 via entrez): RS1000332192 (5:33937596 T>C), RS1000386531 (5:33939179 C>A), RS1000668487 (5:33936257 C>A), RS1001122669 (5:33938584 C>T), RS1001173650 (5:33938851 C>A,T), RS1002412499 (5:33937768 A>G,T), RS1002542192 (5:33939388 TCAAA>T), RS1002879445 (5:33937720 C>T), RS1003201048 (5:33936066 C>A), RS10045759 (5:33934653 T>C), RS1004718578 (5:33935745 A>G), RS1004928967 (5:33939275 G>A,C), RS1005132187 (5:33936001 C>T), RS1006399750 (5:33934585 A>G), RS1007006780 (5:33935001 C>T)

Disease associations

OMIM: gene MIM:609445 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1628472 (SINGLE PROTEIN), CHEMBL4523612 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Relaxin family peptide receptors

Most potent curated ligand interactions (27 total), top 25:

Ligand	Action	Affinity	Parameter
minimised relaxin-3 analogue 2	Full agonist	10.4	pEC50
[G(B24)S]R3/I5	Agonist	10.1	pIC50
relaxin	Full agonist	10.0	pKd
relaxin-3	Full agonist	9.6	pIC50
[125I]relaxin-3 (human)	Full agonist	9.5	pKd
R3(BΔ23-27)R/I5 chimeric peptide	Partial agonist	9.4	pIC50
R3/I5	Full agonist	9.3	pIC50
[125I]relaxin-3-B/INSL5 A chimera	Agonist	9.3	pKd
R3/I5- SmBiT	Agonist	9.2	pKd
DOTA/Eu relaxin-3	Agonist	8.7	pKd
H3 Ac-B10-27(13-17 HC)	Full agonist	8.5	pIC50
europium-labelled relaxin-3-B/INSL5 A chimera	Agonist	8.3	pKd
relaxin-3	Full agonist	8.0	pIC50
compound 4 [PMID: 30824200]	Agonist	7.89	pEC50
R3 B1-22R	Antagonist	7.69	pKi
minimised relaxin-3 analogue 3	Antagonist	7.6	pKi
europium-labelled R3(B1-22R)	Antagonist	7.55	pKd
H3 14s18 stapled B-chain	Full agonist	7.5	pIC50
compound 10d [PMID: 34855388]	Agonist	7.16	pKi
INSL5	Antagonist	7.01	pKi
relaxin-3 (B chain)	Full agonist	6.9	pIC50
H3B10-27(13/17αF)	Agonist	6.83	pKi
relaxin-3 B chain dimer	Full agonist	6.61	pKi
135PAM1	Positive	6.12	pEC50
B1-27	Agonist	5.91	pKi

ChEMBL bioactivities

193 potent at pChembl≥5 of 194 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	EC50	0.1202	nM	CHEMBL4557279
8.85	EC50	1.4	nM	CHEMBL5081158
8.85	EC50	1.4	nM	CHEMBL5094669
8.64	EC50	2.3	nM	CHEMBL5084331
8.51	EC50	3.1	nM	CHEMBL5089949
8.48	EC50	3.311	nM	CHEMBL4557279
8.45	EC50	3.548	nM	CHEMBL4540069
8.37	IC50	4.266	nM	CHEMBL2030700
8.36	EC50	4.365	nM	CHEMBL4781389
8.35	EC50	4.467	nM	CHEMBL4476408
8.35	EC50	4.467	nM	CHEMBL4435599
8.29	IC50	5.129	nM	CHEMBL2030701
8.28	EC50	5.248	nM	CHEMBL4438620
8.25	EC50	5.6	nM	CHEMBL5083969
8.21	EC50	6.166	nM	CHEMBL4761849
8.21	EC50	6.166	nM	CHEMBL4764969
8.11	EC50	7.7	nM	CHEMBL5072593
7.99	EC50	10.2	nM	CHEMBL5081158
7.96	EC50	11	nM	CHEMBL5077251
7.96	Ki	11.1	nM	CHEMBL5185575
7.93	EC50	11.75	nM	CHEMBL4447532
7.91	EC50	12.3	nM	CHEMBL5089949
7.90	IC50	12.59	nM	CHEMBL2030702
7.88	EC50	13.18	nM	CHEMBL4778498
7.88	EC50	13.2	nM	CHEMBL5094670
7.87	EC50	13.6	nM	CHEMBL5078386
7.80	EC50	15.85	nM	CHEMBL4799017
7.74	EC50	18.2	nM	CHEMBL4522365
7.71	EC50	19.5	nM	CHEMBL5080438
7.66	EC50	22	nM	CHEMBL4522365
7.34	Ki	45.71	nM	CHEMBL4761849
7.28	EC50	52.2	nM	CHEMBL5078678
7.28	EC50	53	nM	CHEMBL5094396
7.25	EC50	56.1	nM	CHEMBL5076246
7.17	EC50	67	nM	CHEMBL5075697
7.16	EC50	69.9	nM	CHEMBL5084431
7.16	Ki	68.7	nM	CHEMBL5089949
7.14	EC50	73	nM	CHEMBL5078074
7.13	EC50	74.7	nM	CHEMBL4546426
7.12	Ki	75.86	nM	CHEMBL6132956
7.09	EC50	82	nM	CHEMBL4522365
7.08	EC50	82.3	nM	CHEMBL5078324
7.03	Ki	93.33	nM	CHEMBL4476408
7.01	EC50	98.4	nM	CHEMBL5082272
6.97	Ki	107.2	nM	CHEMBL4438620
6.96	Ki	109.7	nM	CHEMBL2030702
6.96	Ki	109.7	nM	CHEMBL4540069
6.96	Ki	109.7	nM	CHEMBL4764969
6.95	Ki	112.2	nM	CHEMBL2030700
6.95	Ki	112.2	nM	CHEMBL2030701

PubChem BioAssay actives

126 with measured affinity, of 236 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
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-2-benzyl-5-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-11,20-dimethyl-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1632044: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells assessed as ERK1/2 phosphorylation incubated for 5 mins by alphascreen surefire assay	ec50	0.0001	uM
2-[2-(4-cyanophenyl)ethyl]-1-[(E)-(7-ethyl-5-methoxy-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0014	uM
1-[(E)-(5-cyano-7-ethyl-1H-indol-3-yl)methylideneamino]-2-(2-pyridin-3-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0014	uM
1-[(E)-(7-ethyl-5-methoxy-1H-indol-3-yl)methylideneamino]-2-(2-pyridin-3-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0023	uM
methyl 4-[2-[[amino-[(2E)-2-[(5-cyano-7-methyl-1H-indol-3-yl)methylidene]hydrazinyl]methylidene]amino]ethyl]benzoate	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0031	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-2-benzyl-5-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-11,20-dimethyl-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1632039: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay	ec50	0.0035	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,54S,57S,60S,63S,66S,69S,72S,75S,78S,81S,84R)-43-amino-48-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-25,40-bis(4-aminobutyl)-60,78-dibenzyl-16,63,75-tris[(2S)-butan-2-yl]-84-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-54,66-bis(3-carbamimidamidopropyl)-19,57-bis(2-carboxyethyl)-81-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31,69-dimethyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,49,52,55,58,61,64,67,70,73,76,79,82-pentacosaoxo-72-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,50,53,56,59,62,65,68,71,74,77,80,83-pentacosazacyclopentaoctacontane-4-carboxylic acid	661334: Agonist activity at RXFP3 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 6 hrs by beta galactosidase reporter gene assay	ic50	0.0043	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,51S,54S,57S,60S,63S,66S,69S,72S,75S,81R)-81-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-acetamido-3-amino-3-oxopropoxy]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-43-amino-25,40-bis(4-aminobutyl)-54,69-dibenzyl-16,57,66-tris[(2S)-butan-2-yl]-48-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-63,75-bis(3-carbamimidamidopropyl)-19,72-bis(2-carboxyethyl)-51-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31-methyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,50,53,56,59,62,65,68,71,74,77,80-tetracosaoxo-60-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,49,52,55,58,61,64,67,70,73,76,79-tetracosazacyclodooctacontane-4-carboxylic acid	1726174: Agonist activity at RXFP3 (unknown origin) stably expressed in CHO-K1 cells co-transfected with pCRE assessed as inhibition of forskolin-induced cAMP accumulation measured after 6 hrs by beta-galactosidase reporter gene assay	ec50	0.0044	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-2-benzyl-5-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-11,20-dimethyl-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1632039: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay	ec50	0.0045	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-2-benzyl-5-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-11,20-dimethyl-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1632039: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay	ec50	0.0045	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,54S,57S,60S,63S,66S,69S,72S,75S,78S,81S,84R)-43-amino-25,40-bis(4-aminobutyl)-48-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-60,78-dibenzyl-16,63,75-tris[(2S)-butan-2-yl]-84-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-54,66-bis(3-carbamimidamidopropyl)-19,57-bis(2-carboxyethyl)-81-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31,69-dimethyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,49,52,55,58,61,64,67,70,73,76,79,82-pentacosaoxo-72-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,50,53,56,59,62,65,68,71,74,77,80,83-pentacosazacyclopentaoctacontane-4-carboxylic acid	661334: Agonist activity at RXFP3 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 6 hrs by beta galactosidase reporter gene assay	ic50	0.0051	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-2-benzyl-5-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-11,20-dimethyl-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1632039: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay	ec50	0.0052	uM
1-[(E)-(7-ethyl-5-methoxy-1H-indol-3-yl)methylideneamino]-2-[2-(4-fluorophenyl)ethyl]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0056	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,51S,54S,57S,60S,63S,66S,69S,72S,75S,81R)-43-amino-25,40-bis(4-aminobutyl)-54,69-dibenzyl-16,57,66-tris[(2S)-butan-2-yl]-81-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]pentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]-48-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-63,75-bis(3-carbamimidamidopropyl)-19,72-bis(2-carboxyethyl)-51-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31-methyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,50,53,56,59,62,65,68,71,74,77,80-tetracosaoxo-60-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,49,52,55,58,61,64,67,70,73,76,79-tetracosazacyclodooctacontane-4-carboxylic acid	1726174: Agonist activity at RXFP3 (unknown origin) stably expressed in CHO-K1 cells co-transfected with pCRE assessed as inhibition of forskolin-induced cAMP accumulation measured after 6 hrs by beta-galactosidase reporter gene assay	ec50	0.0062	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,51S,54S,57S,60S,63S,66S,69S,72S,75S,81R)-43-amino-25,40-bis(4-aminobutyl)-54,69-dibenzyl-16,57,66-tris[(2S)-butan-2-yl]-81-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-carbamoyloxy-3-(1H-indol-3-yl)propan-2-yl]amino]pentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]-48-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-63,75-bis(3-carbamimidamidopropyl)-19,72-bis(2-carboxyethyl)-51-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31-methyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,50,53,56,59,62,65,68,71,74,77,80-tetracosaoxo-60-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,49,52,55,58,61,64,67,70,73,76,79-tetracosazacyclodooctacontane-4-carboxylic acid	1726174: Agonist activity at RXFP3 (unknown origin) stably expressed in CHO-K1 cells co-transfected with pCRE assessed as inhibition of forskolin-induced cAMP accumulation measured after 6 hrs by beta-galactosidase reporter gene assay	ec50	0.0062	uM
methyl 4-[2-[[amino-[(2E)-2-[(5-methoxy-7-methyl-1H-indol-3-yl)methylidene]hydrazinyl]methylidene]amino]ethyl]benzoate	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0077	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-(2-pyridin-3-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0110	uM
(4S)-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoic acid	1910904: Displacement of [125I]R3/I5 from human RXFP3 expressed in CHO-K1 cells membrane assessed as inhibition constant incubated for 1 hr by microplate scintillation counting analysis	ki	0.0111	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-acetamidoacetyl)amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-2-benzyl-5-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-11,20-dimethyl-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1632039: Agonist activity at human RXFP3 receptor expressed in CHOK1 cells cotransfected with beta-galactosidase assessed as inhibition of forskolin-stimulated cAMP by beta-galactosidase reporter gene assay	ec50	0.0118	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,54S,57S,60S,63S,66S,69S,72S,75S,78S,81S,84R)-43,48-diamino-25,40-bis(4-aminobutyl)-60,78-dibenzyl-16,63,75-tris[(2S)-butan-2-yl]-84-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-54,66-bis(3-carbamimidamidopropyl)-19,57-bis(2-carboxyethyl)-81-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31,69-dimethyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,49,52,55,58,61,64,67,70,73,76,79,82-pentacosaoxo-72-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,50,53,56,59,62,65,68,71,74,77,80,83-pentacosazacyclopentaoctacontane-4-carboxylic acid	661334: Agonist activity at RXFP3 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 6 hrs by beta galactosidase reporter gene assay	ic50	0.0126	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,51S,54S,57S,60S,63S,66S,69S,72S,75S,81R)-43-amino-25,40-bis(4-aminobutyl)-54,69-dibenzyl-16,57,66-tris[(2S)-butan-2-yl]-81-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-hydroxy-3-(1H-indol-3-yl)propan-2-yl]amino]pentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]pentanoyl]amino]-4-methylpentanoyl]amino]-48-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-63,75-bis(3-carbamimidamidopropyl)-19,72-bis(2-carboxyethyl)-51-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31-methyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,50,53,56,59,62,65,68,71,74,77,80-tetracosaoxo-60-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,49,52,55,58,61,64,67,70,73,76,79-tetracosazacyclodooctacontane-4-carboxylic acid	1726174: Agonist activity at RXFP3 (unknown origin) stably expressed in CHO-K1 cells co-transfected with pCRE assessed as inhibition of forskolin-induced cAMP accumulation measured after 6 hrs by beta-galactosidase reporter gene assay	ec50	0.0132	uM
2-[2-(4-cyanophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0132	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-[2-(4-nitrophenyl)ethyl]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0136	uM
(4R,7S,10S,13S,16S,19S,22S,25S,28S,31S,37S,40S,43R,48R,51S,54S,57S,60S,63S,66S,69S,72S,75S,81R)-43-amino-25,40-bis(4-aminobutyl)-81-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-54,69-dibenzyl-16,57,66-tris[(2S)-butan-2-yl]-48-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamoyl]-63,75-bis(3-carbamimidamidopropyl)-19,72-bis(2-carboxyethyl)-51-[(1R)-1-hydroxyethyl]-10,13,22,28-tetrakis(hydroxymethyl)-37-(1H-indol-3-ylmethyl)-31-methyl-7-(2-methylpropyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,50,53,56,59,62,65,68,71,74,77,80-tetracosaoxo-60-propan-2-yl-1,2,45,46-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,49,52,55,58,61,64,67,70,73,76,79-tetracosazacyclodooctacontane-4-carboxylic acid	1726174: Agonist activity at RXFP3 (unknown origin) stably expressed in CHO-K1 cells co-transfected with pCRE assessed as inhibition of forskolin-induced cAMP accumulation measured after 6 hrs by beta-galactosidase reporter gene assay	ec50	0.0158	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(7-ethyl-5-hydroxy-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0182	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(7-ethyl-5-methoxy-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0195	uM
2-[2-(4-fluorophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0522	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-(2-thiophen-3-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0530	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-[2-(4-methoxyphenyl)ethyl]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0561	uM
2-[2-(4-iodophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0670	uM
2-[2-(4-bromophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0699	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-(2-thiophen-2-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0730	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0747	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(5-cyano-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0823	uM
2-[2-[4-(dimethylamino)phenyl]ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.0984	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-(2-phenylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.2240	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-[2-(4-methylphenyl)ethyl]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.2380	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(5-cyano-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.2530	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-(2-pyridin-4-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.2730	uM
2-[2-(3,4-dichlorophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.3060	uM
methyl 3-[(E)-[[N’-[2-(4-chlorophenyl)ethyl]carbamimidoyl]hydrazinylidene]methyl]-1H-indole-5-carboxylate	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.3120	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(5-nitro-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.3170	uM
N-[4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]phenyl]-5-oxo-1-(pyridin-3-ylmethyl)pyrrolidine-3-carboxamide	1910921: Antagonist activity at human RXFP3 expressed in CHO-K1 cells assessed as inhibition of relaxin-3 stimulated ERK1/2 phosphorylation preincubated for 15 mins followed by relaxin-3 addition for 5 mins	ic50	0.5610	uM
(4S)-4-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(3S,6S,9S,12S,16Z,21S)-3-benzyl-6-[(2S)-butan-2-yl]-21-[[(2S)-1-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]-12,21-dimethyl-2,5,8,11-tetraoxo-9-propan-2-yl-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1632038: Displacement of Eu-H3/15 from human RXFP3 receptor expressed in CHOK1 cells by time-resolved fluorescent whole cell binding assay	ki	0.5754	uM
(4S)-4-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(3S,6S,9S,12S,16Z,21S)-3-benzyl-6-[(2S)-butan-2-yl]-21-[[(2S)-1-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]-12,21-dimethyl-2,5,8,11-tetraoxo-9-propan-2-yl-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1632038: Displacement of Eu-H3/15 from human RXFP3 receptor expressed in CHOK1 cells by time-resolved fluorescent whole cell binding assay	ki	0.6026	uM
2-[2-(4-chlorophenyl)ethyl]-1-[(E)-(7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.6470	uM
(4S)-4-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[2-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	661336: Displacement of europium-labelled H3 relaxin-B chain/INSL-5 chain from RXFP3 expressed in CHO-K1 cells	ki	0.7413	uM
2-[2-(2-chlorophenyl)ethyl]-1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.7970	uM
2-[2-(3,4-dichlorophenyl)ethyl]-1-[(E)-(5-hydroxy-7-methyl-1H-indol-3-yl)methylideneamino]guanidine	1603003: Agonist activity at human RXFP3 expressed in CHOK1 cells assessed as inhibition of forskolin-stimulated intracellular cAMP accumulation preincubated for 30 mins followed by forskolin-stimulation and measured after 30 mins by HTRF assay	ec50	0.8000	uM
1-[(E)-(5-methoxy-7-methyl-1H-indol-3-yl)methylideneamino]-2-(2-pyridin-2-ylethyl)guanidine	1811599: Agonist activity at human RXFP3 expressed in human CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 1.5 hrs by TR-FRET assay	ec50	0.8550	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Phthalic Acids	increases methylation	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

38 unique, capped per target: 21 functional, 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2034650	Functional	Agonist activity at RXFP3 expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 6 hrs by beta galactosidase reporter gene assay	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
CHEMBL2034745	Binding	Displacement of europium-labelled H3 relaxin-B chain/INSL-5 chain from RXFP3 expressed in CHO-K1 cells	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

Cellosaurus cell lines

4 cell lines: 2 spontaneously immortalized cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV78	cAMP Hunter CHO-K1 RXFP3 Gi	Spontaneously immortalized cell line	Female
CVCL_KZ06	PathHunter CHO-K1 RXFP3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB29	PathHunter U2OS RXFP3 Total GPCR Internalization	Cancer cell line	Female
CVCL_ZK20	Tango RLN3R1-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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