GHSR

Summary

GHSR (growth hormone secretagogue receptor, HGNC:4267) is a protein-coding gene on chromosome 3q26.31, encoding Growth hormone secretagogue receptor type 1 (Q92847). G-protein-coupled receptor specific to ghrelin, an appetite-regulating peptide hormone commonly found in stomach.

This gene encodes a member of the G-protein coupled receptor family. The encoded protein may play a role in energy homeostasis and regulation of body weight. Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a. Mutations in this gene are associated with autosomal idiopathic short stature.

Source: NCBI Gene 2693 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature due to GHSR deficiency (Strong, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 289 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 113 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_198407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4267
Approved symbol	GHSR
Name	growth hormone secretagogue receptor
Location	3q26.31
Locus type	gene with protein product
Status	Approved
Aliases	GHS-R1a, GHS-R, GHSR-1a
Ensembl gene	ENSG00000121853
Ensembl biotype	protein_coding
OMIM	601898
Entrez	2693

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000241256, ENST00000427970

RefSeq mRNA: 2 — MANE Select: NM_198407 NM_004122, NM_198407

CCDS: CCDS3218, CCDS46959

Canonical transcript exons

ENST00000241256 — 2 exons

Exon	Start	End
ENSE00000826263	172447618	172448456
ENSE00000826264	172443291	172445465

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 68.70.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	68.70	gold quality
islet of Langerhans	UBERON:0000006	68.43	gold quality
adenohypophysis	UBERON:0002196	66.05	gold quality
endothelial cell	CL:0000115	64.04	gold quality
oocyte	CL:0000023	62.82	gold quality
buccal mucosa cell	CL:0002336	56.49	silver quality
heart right ventricle	UBERON:0002080	56.34	gold quality
nasal cavity epithelium	UBERON:0005384	54.23	gold quality
nipple	UBERON:0002030	53.58	gold quality
trachea	UBERON:0003126	53.54	gold quality
dorsal root ganglion	UBERON:0000044	53.49	gold quality
layer of synovial tissue	UBERON:0007616	53.49	gold quality
urethra	UBERON:0000057	53.35	gold quality
inferior vagus X ganglion	UBERON:0005363	53.25	gold quality
trigeminal ganglion	UBERON:0001675	53.19	gold quality
ventral tegmental area	UBERON:0002691	53.18	gold quality
saphenous vein	UBERON:0007318	53.13	gold quality
pericardium	UBERON:0002407	52.99	gold quality
thymus	UBERON:0002370	52.81	gold quality
mammalian vulva	UBERON:0000997	52.78	gold quality
synovial joint	UBERON:0002217	52.78	gold quality
penis	UBERON:0000989	52.68	gold quality
medulla oblongata	UBERON:0001896	52.65	gold quality
pylorus	UBERON:0001166	52.63	gold quality
renal medulla	UBERON:0000362	52.60	gold quality
dorsal plus ventral thalamus	UBERON:0001897	52.48	gold quality
superior surface of tongue	UBERON:0007371	52.45	gold quality
superior vestibular nucleus	UBERON:0007227	52.39	gold quality
pons	UBERON:0000988	52.30	gold quality
subthalamic nucleus	UBERON:0001906	52.23	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	10.83
E-GEOD-81547	yes	5.01
E-GEOD-81608	yes	4.67
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SON

Literature-anchored findings (GeneRIF, showing 40)

• Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity (PMID:12045256)
• Review. This review will summarize data regarding the structure of the GHS-R gene and the protein encoded, reports investigating the expression and control of the GHS-R in various tissues, and studies of the underlying transcriptional mechanisms. (PMID:12511847)
• The presence of ligand and receptor of the ghrelin signaling system within the human ovary opens up the possibility of a potential regulatory role of this novel molecule in ovarian function under physiological and pathophysiological conditions. (PMID:12574228)
• Constitutive overexpression of GHSR can up-regulate basal signaling activity in the GHRH/GH axis and reduce adiposity without affecting other GHSR-mediated signals. (PMID:14701677)
• no conclusive evidence for an involvement of the ghrelin receptor gene in body weight regulation or short normal stature (PMID:14715843)
• results demonstrate that ghrelin and the type 1a growth hormone secretagogue receptor are expressed in adult human testis and testicular tumors (PMID:14715878)
• Specific ghrelin (GHS) binding sites, other than GHS-R1a and 1b, are present in human prostatic neoplasms. Ghrelin, in addition to des-acyl ghrelin, exerts different effects on cell proliferation in prostate carcinoma cell lines. (PMID:14763915)
• genetic variations in the GHS-R1a gene are not the main regulators of IGF-I levels (PMID:15080774)
• potential use of ghrelin and GHS-R agonists in the management of disease-associated cachexia. (PMID:15232612)
• ghrelin receptor, neurotensin receptor 2 and GPR39 display an unusually high degree of constitutive activity, determined by an aromatic cluster on the inner face of the extracellular ends of TMs VI and VII (PMID:15383539)
• ovarian surface epithelium and related tumors are potential targets for systemic or locally produced ghrelin because they express the functional type 1a GHS-R (PMID:15585554)
• Single nucleotide polymorphisms and haplotypes within the GHSR region are involved in the pathogenesis of human obesity. (PMID:15616037)
• Downregulation of GHS-R1a and high levels of GHS-R1b transcripts are associated with adrenal tumors (PMID:16020971)
• the 171T/C polymorphism of the ghrelin receptor gene in patients diagnosed with Eating disorders (PMID:16362631)
• Review concludes that selective lack of ghrelin receptor constitutive signaling leads to a syndrome characterized not only by short stature, but also by obesity that apparently develops during puberty. (PMID:16511600)
• A GHSR missense mutation segregates with short stature resulting in decreased cell-surface expression of the receptor and selective impairment of the constitutive activity of GHSR, while preserving its ability to respond to ghrelin. (PMID:16511605)
• Ghrelin and the growth hormone secretagogue receptor have roles in astrocytoma motility (PMID:16527811)
• Variants in ghrelin receptor are associated with parameters of left ventricular mass and geometry independent of blood pressure and body mass in general population and may be involved in pathogenesis of left ventricular hypertrophy. (PMID:16567594)
• ghrelin, through GHSR-1a, activates the Elk1 transcriptional factor and ERK1/2 by a PLC- and PKCepsilon-dependent pathway (PMID:16582936)
• This overview focuses on recent studies of tissue distribution, expression regulation and the multiple actions of the ghrelin receptor (GHS-R) and its involvement in the control of energy homeostasis and its ability to stimulate food intake and adiposity. (PMID:16787234)
• NMU & its cancer-specific receptors NTSR1 & GHSR1b, as well as its target genes, are overexpressed in lung cancer and in cell lines, and that those gene products play indispensable roles in the growth and progression of lung cancer cells. (PMID:17018595)
• Investigation of whether the full-length GRLN-R physically interacts with its truncated splice variant GHS-R1b (PMID:17229547)
• Adenosine is not a direct GHSR agonist. In human embryonic kidney 293s (HEK) cells expressing GHSR, adenosine activates endogenously expressed A(2B)R resulting in calcium mobilization. (PMID:17428235)
• This study demonstrates the cyclical expression of GHS-R and ghrelin in human endometrium. (PMID:17494105)
• These findings demonstrate in a defined system that unacylated ghrelin does not antagonize activation of the GHS-R by ghrelin. (PMID:17601657)
• HepG2 cells do not express a GHS-R1a-type ghrelin receptor (PMID:17885924)
• Our results showed that ghrelin receptor was expressed in cancers throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer cells. (PMID:18064392)
• A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height. (PMID:18375957)
• Higher GHSR-1a is associated with Crohn’s disease. (PMID:18425803)
• higher expression of GHSR-1a in the ACTH-dependent Cushing patients responsive to GHRP-6, suggesting an association between receptor gene expression and in vivo response to the secretagogue (PMID:18426818)
• Data suggest that expression of prostanoid receptors (prostaglandin E2 EP3-I, prostacyclin, and thromboxane A2 receptors) in vascular inflammation could influence cell responses dependent on the constitutive activation of ghrelin receptors. (PMID:18573679)
• Common variation in GHSR is not associated with body size in U.K. adults or children. (PMID:18647811)
• Polymorphisms in the GHSR promoter may modify changes in body weight during long-term lifestyle intervention and affect ghrelin receptor signalling through modulation of GHSR gene expression. (PMID:18698404)
• This first study of single nucleotide polymorphisms (SNPs) of the GHS-R1A gene shows that association with heavy alcohol consumption correlates with body mass in heavy alcohol consuming individuals. (PMID:18828808)
• Variants of the ghrelin and GHSR genes are not major contributors to height variation in a French population. (PMID:18945286)
• The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women. (PMID:19024096)
• GHRH interacts with ghrelin receptor GHS-R1a, and, in consequence, modifies the ghrelin-associated intracellular signaling pathway (PMID:19088192)
• Common polymorphisms in ghrelin and its receptor genes are not major contributors to the development of polygenic obesity, although common variants may alter body weight and eating behavior. (PMID:19165163)
• beta-arrestins and c-Src are implicated in the activation of Akt in response to ghrelin through the GHS-R1a (PMID:19262695)
• epistatic effects of five candidate genes, including ADIPOQ, ENPP1, GHSR, PPAR and TCF7L2, are significantly associated with the risk of DN amongst Taiwanese T2D individuals. (PMID:19506043)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ghsra	ENSDARG00000056230
danio_rerio	ghsrb	ENSDARG00000057117
mus_musculus	Ghsr	ENSMUSG00000051136
rattus_norvegicus	Ghsr	ENSRNOG00000024119

Paralogs (15): NTSR1 (ENSG00000101188), BRS3 (ENSG00000102239), MLNR (ENSG00000102539), GRPR (ENSG00000126010), NMUR2 (ENSG00000132911), NMBR (ENSG00000135577), EDNRB (ENSG00000136160), EDNRA (ENSG00000151617), NTSR2 (ENSG00000169006), GPR37L1 (ENSG00000170075), GPR37 (ENSG00000170775), NMUR1 (ENSG00000171596), GPR148 (ENSG00000173302), TRHR (ENSG00000174417), GPR39 (ENSG00000183840)

Protein

Protein identifiers

Growth hormone secretagogue receptor type 1 — Q92847 (reviewed: Q92847)

Alternative names: GH-releasing peptide receptor, Ghrelin receptor

All UniProt accessions (1): Q92847

UniProt curated annotations — full annotation on UniProt →

Function. G-protein-coupled receptor specific to ghrelin, an appetite-regulating peptide hormone commonly found in stomach. Upon activation, stimulates appetite and promotes growth hormone secretion. Also binds other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692, 429, MK-0677, adenosine).

Subunit / interactions. Interacts with the heterotrimeric G-protein complex composed of 3 units, alpha, beta and gamma; this complex may consist of GNB1 and GNG2.

Subcellular location. Cell membrane.

Tissue specificity. Pituitary and hypothalamus.

Disease relevance. Growth hormone deficiency, isolated partial (GHDP) [MIM:615925] A disorder characterized by partial growth hormone deficiency resulting in growth delay and short stature, sometimes associated with recurrent episodes of abdominal pain, vomiting, ketosis and hypoglycemia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by octanoylated ghrelin; octanoylation is essential for full activation of the receptor. Stimulated by anamorelin, which binds to the same binding sites as ghrelin.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q92847-1	1A	yes
Q92847-2	1B

RefSeq proteins (2): NP_004113, NP_940799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR003905	GHS-R/MTLR	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (64 total): mutagenesis site 18, helix 14, topological domain 8, transmembrane region 7, binding site 5, sequence variant 3, glycosylation site 2, splice variant 2, strand 2, chain 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9UY3	ELECTRON MICROSCOPY	2.52
9V2N	ELECTRON MICROSCOPY	2.63
7NA7	ELECTRON MICROSCOPY	2.7
7NA8	ELECTRON MICROSCOPY	2.7
7W2Z	ELECTRON MICROSCOPY	2.8
7F9Y	ELECTRON MICROSCOPY	2.9
8JSR	ELECTRON MICROSCOPY	2.9
7F83	X-RAY DIFFRACTION	2.94
7F9Z	ELECTRON MICROSCOPY	3.2
6KO5	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92847-F1	81.75	0.50

Antibody-complex structures (SAbDab): 7 — 6KO5, 7F9Y, 7F9Z, 7NA7, 7NA8, 7W2Z, 8JSR

Functional residue map

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

Ligand- & substrate-binding residues (5): 178; 181; 213; 214; 286

Disulfide bonds (1): 116–198

Glycosylation sites (2): 13, 27

Mutagenesis-validated functional residues (18):

Position	Phenotype
99	impairs receptor activity stimulated by anamorelin.
102	impairs receptor activity stimulated by anamorelin.
103	impairs receptor activity stimulated by anamorelin.
120	impairs receptor activity stimulated by anamorelin.
124	abolishes receptor activity stimulated by anamorelin. abolishes receptor activity stimulated by ghrelin.
178	impairs receptor activity stimulated by anamorelin.
210	impairs receptor activity stimulated by anamorelin. impairs receptor activity stimulated by ghrelin.
213	impairs receptor activity stimulated by anamorelin.
217	impairs receptor activity stimulated by anamorelin.
276	impairs receptor activity stimulated by ghrelin.
279	impairs receptor activity stimulated by ghrelin.
283	abolishes receptor activity stimulated by anamorelin. impairs receptor activity stimulated by ghrelin.
286	impairs receptor activity stimulated by anamorelin. abolishes receptor activity stimulated by ghrelin.
302	abolishes receptor activity stimulated by ghrelin.
305	impairs receptor activity stimulated by ghrelin.
305	impairs receptor activity stimulated by anamorelin.
309	impairs receptor activity stimulated by anamorelin.
312	impairs receptor activity stimulated by anamorelin. impairs receptor activity stimulated by ghrelin.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 349 (showing top): GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INFLAMMATORY_RESPONSE, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (54): G protein-coupled receptor signaling pathway (GO:0007186), spermatogenesis (GO:0007283), learning or memory (GO:0007611), actin polymerization or depolymerization (GO:0008154), adult feeding behavior (GO:0008343), response to hormone (GO:0009725), hormone-mediated signaling pathway (GO:0009755), negative regulation of norepinephrine secretion (GO:0010700), growth hormone secretion (GO:0030252), response to food (GO:0032094), negative regulation of appetite (GO:0032099), positive regulation of appetite (GO:0032100), response to follicle-stimulating hormone (GO:0032354), response to estradiol (GO:0032355), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), cellular response to insulin stimulus (GO:0032869), ghrelin secretion (GO:0036321), positive regulation of multicellular organism growth (GO:0040018), regulation of hindgut contraction (GO:0043134), positive regulation of insulin-like growth factor receptor signaling pathway (GO:0043568), positive regulation of fatty acid metabolic process (GO:0045923), negative regulation of insulin secretion (GO:0046676), decidualization (GO:0046697), insulin-like growth factor receptor signaling pathway (GO:0048009), negative regulation of inflammatory response (GO:0050728), regulation of synapse assembly (GO:0051963), regulation of transmission of nerve impulse (GO:0051969), regulation of growth hormone secretion (GO:0060123), response to growth hormone (GO:0060416), cellular response to lipopolysaccharide (GO:0071222), response to dexamethasone (GO:0071548), negative regulation of locomotion involved in locomotory behavior (GO:0090327), cellular response to thyroid hormone stimulus (GO:0097067), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), postsynaptic modulation of chemical synaptic transmission (GO:0099170), regulation of postsynapse organization (GO:0099175), positive regulation of small intestinal transit (GO:0120058), response to L-glutamate (GO:1902065)

GO Molecular Function (7): growth hormone secretagogue receptor activity (GO:0001616), G protein-coupled receptor activity (GO:0004930), growth hormone-releasing hormone receptor activity (GO:0016520), peptide hormone binding (GO:0017046), identical protein binding (GO:0042802), protein binding (GO:0005515), hormone binding (GO:0042562)

GO Cellular Component (9): plasma membrane (GO:0005886), cell surface (GO:0009986), neuron projection (GO:0043005), membrane raft (GO:0045121), synaptic membrane (GO:0097060), Schaffer collateral - CA1 synapse (GO:0098685), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	4
G protein-coupled receptor activity	3
cellular anatomical structure	3
signal transduction	2
response to chemical	2
peptide hormone secretion	2
regulation of appetite	2
binding	2
developmental process involved in reproduction	1
male gamete generation	1
behavior	1
cognition	1
actin filament organization	1
feeding behavior	1
adult behavior	1
response to endogenous stimulus	1
cellular response to hormone stimulus	1
regulation of norepinephrine secretion	1
negative regulation of catecholamine secretion	1
norepinephrine secretion	1
response to nutrient levels	1
negative regulation of response to food	1
positive regulation of response to food	1
response to gonadotropin	1
response to lipid	1
response to oxygen-containing compound	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
response to insulin	1
cellular response to peptide hormone stimulus	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1

Protein interactions and networks

STRING

1072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GHSR	GHRL	Q9UBU3	999
GHSR	GHRH	P01286	973
GHSR	MBOAT4	Q96T53	949
GHSR	GHRHR	Q02643	888
GHSR	SST	P01166	887
GHSR	GH1	P01241	877
GHSR	CORT	O00230	867
GHSR	MLN	P12872	866
GHSR	MC3R	P41968	849
GHSR	AGRP	O00253	814
GHSR	POMC	P01189	792
GHSR	LEAP2	Q969E1	784
GHSR	LEP	P41159	766
GHSR	NMU	P48645	760
GHSR	IGF1	P01343	757

IntAct

2 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (9): KSR1 (Negative Genetic), GHSR (Positive Genetic), GHSR (Positive Genetic), P2RY6 (Positive Genetic), UCK2 (Positive Genetic), GHSR (FRET), GHSR (FRET), SIGMAR1 (FRET), GHSR (Reconstituted Complex)

ESM2 similar proteins: A5A4K9, A5A4L1, B2ZI34, F1MV99, O08725, O08786, O42329, O43193, O62709, O97772, P11616, P21451, P21729, P24053, P25099, P26684, P28088, P28190, P28646, P30542, P30550, P30551, P30872, P30873, P32238, P33534, P34970, P34975, P35342, P41144, P41145, P47745, P47751, P48302, P52500, P60893, P60894, P60895, Q2KIP6, Q49LX5

Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, O08725, O17239, O42179, O43193, O55040, O88319, O93603, P19020, P20789, P20905, P21917, P24628, P30989, P35367, P49683, P58826, P79291, Q09388, Q25188, Q28553, Q58CW4, Q5QD24, Q63384, Q7JQF1, Q8BZ39, Q8ITC7, Q90WY4, Q923Y8, Q92847, Q93126, Q95254, Q99P50, Q9ESQ4, Q9GZQ4, Q9HB89, Q9JJI5, Q9JJS7

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
GHRL	up-regulates	GHSR	binding
GHSR	“up-regulates activity”	GNAS	binding
GHSR	“up-regulates activity”	GNAL	binding
GHSR	“up-regulates activity”	GNAI1	binding
GHSR	“up-regulates activity”	GNAI3	binding
GHSR	“up-regulates activity”	GNAO1	binding
GHSR	“up-regulates activity”	GNAZ	binding
GHSR	“up-regulates activity”	GNAQ	binding
GHSR	“up-regulates activity”	GNA14	binding
Ibutamoren	“up-regulates activity”	GHSR	“chemical activation”
CORT	up-regulates	GHSR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	187
Likely benign	65
Benign	22

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
7633	NM_198407.2(GHSR):c.6G>A (p.Trp2Ter)	Pathogenic
3252244	NM_198407.2(GHSR):c.517T>C (p.Cys173Arg)	Likely pathogenic

SpliceAI

574 predictions. Top by Δscore:

Variant	Effect	Δscore
3:172447702:T:TA	donor_gain	1.0000
3:172446944:T:TA	donor_gain	0.9900
3:172447616:AC:A	donor_gain	0.9900
3:172447617:CC:C	donor_gain	0.9900
3:172447617:CCCAG:C	donor_gain	0.9900
3:172446924:T:TA	donor_gain	0.9800
3:172447651:C:A	donor_gain	0.9800
3:172445463:CAG:C	acceptor_gain	0.9700
3:172446924:TC:T	donor_gain	0.9600
3:172447613:CCCA:C	donor_loss	0.9600
3:172447614:CCA:C	donor_loss	0.9600
3:172447615:CA:C	donor_loss	0.9600
3:172447616:A:AT	donor_loss	0.9600
3:172445466:C:CC	acceptor_gain	0.9500
3:172446926:A:AC	donor_gain	0.9500
3:172446927:C:CC	donor_gain	0.9500
3:172447687:T:TA	donor_gain	0.9500
3:172447772:CACCA:C	donor_gain	0.9500
3:172447774:CCA:C	donor_gain	0.9500
3:172447776:A:AC	donor_gain	0.9400
3:172447777:TG:T	donor_gain	0.9400
3:172447611:GAC:G	donor_loss	0.9300
3:172447772:CA:C	donor_gain	0.9300
3:172445318:C:CC	acceptor_gain	0.9200
3:172447612:ACC:A	donor_loss	0.9200
3:172447616:A:AC	donor_gain	0.9200
3:172447617:C:CC	donor_gain	0.9200
3:172447622:CATTT:C	donor_gain	0.9200
3:172447626:T:TC	donor_gain	0.9200
3:172445464:AGCT:A	acceptor_gain	0.9100

AlphaMissense

2387 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:172448000:G:C	S138R	0.999
3:172448000:G:T	S138R	0.999
3:172448002:T:G	S138R	0.999
3:172448162:G:C	S84R	0.999
3:172448162:G:T	S84R	0.999
3:172448164:T:G	S84R	0.999
3:172445303:G:T	P320H	0.998
3:172445429:G:C	P278R	0.998
3:172445429:G:T	P278H	0.998
3:172445446:G:C	F272L	0.998
3:172445446:G:T	F272L	0.998
3:172445448:A:G	F272L	0.998
3:172448087:C:A	W109C	0.998
3:172448087:C:G	W109C	0.998
3:172448148:T:A	D89V	0.998
3:172448148:T:C	D89G	0.998
3:172448148:T:G	D89A	0.998
3:172448245:C:G	G57R	0.998
3:172445303:G:C	P320R	0.997
3:172445304:G:A	P320S	0.997
3:172445305:G:C	N319K	0.997
3:172445305:G:T	N319K	0.997
3:172445317:A:C	S315R	0.997
3:172445317:A:T	S315R	0.997
3:172445319:T:G	S315R	0.997
3:172445414:C:G	R283P	0.997
3:172447821:C:G	C198S	0.997
3:172447822:A:G	C198R	0.997
3:172447822:A:T	C198S	0.997
3:172447992:C:G	R141P	0.997

dbSNP variants (sampled 300 via entrez): RS1000211466 (3:172444671 T>G), RS1000263913 (3:172444336 A>G), RS1000547641 (3:172449791 A>G), RS1000564585 (3:172444458 T>G), RS1001500672 (3:172448814 A>G), RS1001802128 (3:172443848 T>C), RS1001910561 (3:172450375 T>C), RS1001931766 (3:172449911 G>A,T), RS1002252189 (3:172449166 T>C), RS1003043912 (3:172446827 T>C), RS1003515589 (3:172446543 G>A,T), RS1003526089 (3:172448779 C>T), RS1003985039 (3:172449120 A>G), RS1004821824 (3:172448374 G>A,C), RS1005434019 (3:172444983 T>A)

Disease associations

OMIM: gene MIM:601898 | disease phenotypes: MIM:615925, MIM:603233

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature due to GHSR deficiency	Strong	Autosomal dominant

Mondo (2): short stature due to GHSR deficiency (MONDO:0014403), pseudohypoparathyroidism type 1B (MONDO:0011301)

Orphanet (2): Short stature due to GHSR deficiency (Orphanet:314811), Pseudohypoparathyroidism type 1B (Orphanet:94089)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0001510	Growth delay
HP:0001943	Hypoglycemia
HP:0001946	Ketosis
HP:0002013	Vomiting
HP:0002027	Abdominal pain
HP:0002750	Delayed skeletal maturation
HP:0004322	Short stature
HP:0004323	Abnormality of body weight
HP:0004325	Decreased body weight
HP:0008897	Postnatal growth retardation
HP:0012506	Small pituitary gland
HP:0030353	Decreased circulating serum insulin-like growth factor 1 concentration

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000817_180	Height	3.000000e-18
GCST000817_4	Height	7.000000e-11
GCST001956_64	Height	1.000000e-12
GCST002647_96	Height	3.000000e-23
GCST002702_83	Height	1.000000e-07
GCST007576_385	Chronotype	1.000000e-10
GCST008399_12	Cocaine dependence	5.000000e-06
GCST008839_455	Height	2.000000e-24
GCST009391_154	Metabolite levels	5.000000e-06
GCST012227_1007	Hip circumference adjusted for BMI	3.000000e-08
GCST90000025_677	Appendicular lean mass	9.000000e-64

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0010486	glucuronate measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4616 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

113 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 376,008 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1163	ATAZANAVIR	4	22,094
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1198857	VILANTEROL	4	2,552
CHEMBL1200438	TIOCONAZOLE	4	15,162
CHEMBL1200515	DESERPIDINE	4	2,483
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1201271	BUCLIZINE	4	5,799
CHEMBL1201284	CINACALCET	4	5,917
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL1201309	NAFARELIN	4
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1287853	FEDRATINIB	4
CHEMBL1292	CLOFAZIMINE	4
CHEMBL1303	ROTIGOTINE	4
CHEMBL13280	FLUNITRAZEPAM	4
CHEMBL1346	DARIFENACIN	4
CHEMBL1360	ATRACURIUM	4
CHEMBL1401	NITAZOXANIDE	4
CHEMBL1423	PIMOZIDE	4
CHEMBL1544	LIOTHYRONINE	4
CHEMBL1617	RIFAXIMIN	4

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2232165	GHSR		0.00	0
rs2948694	GHSR		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Ghrelin receptor

Most potent curated ligand interactions (26 total), top 25:

Ligand	Action	Affinity	Parameter
[125I][His9]ghrelin (human)	Full agonist	9.4	pKd
[125I][Tyr4]ghrelin (human)	Full agonist	9.4	pKd
ibutamoren	Full agonist	9.34	pKi
pralmorelin	Full agonist	9.3	pKi
anamorelin	Agonist	9.24	pKi
[35S]ibutamoren	Full agonist	9.2	pKd
SM-130,686	Partial agonist	8.92	pIC50
HM01	Agonist	8.85	pKi
PF-05190457	Antagonist	8.85	pKi
wFw-Isn-NH2	Partial agonist	8.41	pEC50
GSK1614343	Antagonist	8.4	pIC50
GHRP-6	Full agonist	8.34	pEC50
[18F]AQ-12	Antagonist	8.33	pKi
JMV3008	Antagonist	8.25	pIC50
liver enriched antimicrobial peptide 2	Antagonist	8.22	pIC50
[125I]Tyr-Ala-hexarelin	Full agonist	8.2	pKd
Abbott 14c	Antagonist	8.15	pIC50
ghrelin	Full agonist	8.1	pKi
BIM 28163	Antagonist	8.09	pKi
[des-octanoyl]ghrelin	Full agonist	7.9	pKi
examorelin	Full agonist	7.89	pKd
macimorelin	Agonist	7.81	pIC50
YIL781	Antagonist	7.77	pKi
L-692,429	Agonist	7.59	pEC50
[D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P	Antagonist	7.35	pKd

Binding affinities (BindingDB)

142 measured of 152 human assays (152 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[(benzyloxy)methyl]-5-(4-{[(4-nitrophenyl)methyl]amino}phenyl)pyrimidine-2,4-diamine	IC50	0.2 nM
N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-4H-1,2,4-triazol-3-yl}ethyl]piperidine-4-carboxamide	IC50	0.3 nM
6-[(benzyloxy)methyl]-5-(4-{[(4-methanesulfonylphenyl)methyl]amino}phenyl)pyrimidine-2,4-diamine	IC50	0.3 nM
N-[(1R)-1-{4-[(2,4-dimethoxyphenyl)methyl]-5-[2-(1H-indol-3-yl)ethyl]-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]piperidine-4-carboxamide	IC50	0.5 nM
N-[(1R)-1-[5-[(1R)-1-acetamido-2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]pyridine-2-carboxamide	IC50	0.6 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
N-[(1R)-2-(1H-indol-3-yl)-1-{4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-4H-1,2,4-triazol-3-yl}ethyl]piperidine-4-carboxamide	IC50	0.6 nM
6-[(benzyloxy)methyl]-5-(4-{[(4-nitrophenyl)amino]methyl}phenyl)pyrimidine-2,4-diamine	IC50	0.8 nM
N-[(1R)-1-{4-[(2,4-dimethoxyphenyl)methyl]-5-(2-phenylethyl)-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]piperidine-4-carboxamide	IC50	0.9 nM
6-[(benzyloxy)methyl]-5-[4-({[4-(trifluoromethane)sulfonylphenyl]methyl}amino)phenyl]pyrimidine-2,4-diamine	IC50	1 nM
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl (3R)-3-hydroxypyrrolidine-1-carboxylate	EC50	1 nM
1-(4-{[(4-{2,4-diamino-6-[(benzyloxy)methyl]pyrimidin-5-yl}phenyl)amino]methyl}phenyl)ethan-1-one	IC50	1.2 nM
N-[(1R)-1-[5-[(1R)-1-acetamido-2-phenylethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]pyridine-2-carboxamide	IC50	1.3 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
N-[(1R)-1-[5-[(1R)-1-acetamido-2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]-2-amino-2-methylpropanamide	IC50	1.4 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
Ghrelin	EC50	1.4 nM
6-[(benzyloxy)methyl]-5-(4-{[(2-chloropyridin-4-yl)methyl]amino}phenyl)pyrimidine-2,4-diamine	IC50	1.5 nM
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl N-(4-hydroxybutyl)carbamate	EC50	1.9 nM
N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-phenyl-4H-1,2,4-triazol-3-yl}ethyl]piperidine-4-carboxamide	EC50	2.3 nM
5-(4-{[(3,5-difluoro-4-methanesulfonylphenyl)methyl]amino}phenyl)-6-ethylpyrimidine-2,4-diamine	IC50	2.4 nM
(3S)-N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-4H-1,2,4-triazol-3-yl}ethyl]piperidine-3-carboxamide	EC50	2.5 nM
4-{[(4-{2,4-diamino-6-[(benzyloxy)methyl]pyrimidin-5-yl}phenyl)amino]methyl}benzonitrile	IC50	2.8 nM
6-[(benzyloxy)methyl]-5-[4-({[4-(trifluoromethyl)phenyl]methyl}amino)phenyl]pyrimidine-2,4-diamine	IC50	2.9 nM
N-[(1R)-1-[5-[(1R)-1-acetamido-2-phenylethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]-2-hydroxyacetamide	IC50	3 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl N-(2-hydroxyethyl)carbamate	EC50	3 nM
2-amino-N-[(1R)-1-[5-[(1R)-1-formamido-2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]-2-methylpropanamide	IC50	3.2 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl (3R)-3-acetamidopyrrolidine-1-carboxylate	EC50	3.3 nM
N-[(1R)-1-[5-[(1R)-1-formamido-2-phenylethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]pyridine-2-carboxamide	IC50	3.4 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
(2S)-N-[(1R)-1-[5-[(1R)-1-acetamido-2-phenylethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]-2-(1H-indol-3-yl)ethyl]morpholine-2-carboxamide	IC50	3.4 nM	US-8546435: Triazole derivatives with improved receptor activity and bioavailability properties as ghrelin antagonists of growth hormone secretagogue receptors
6-ethyl-5-(4-{(4-methanesulfonylphenyl)methylamino}phenyl)pyrimidine-2,4-diamine	IC50	3.7 nM
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl N-(4-hydroxybutyl)-N-methylcarbamate	EC50	3.8 nM
2-amino-N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-4H-1,2,4-triazol-3-yl}ethyl]-2-methylpropanamide	KD	4 nM
5-(3-chloro-4-{[(4-methanesulfonylphenyl)methyl]amino}phenyl)-6-ethylpyrimidine-2,4-diamine	IC50	4.2 nM
N-[(1R)-1-{4-[(2,4-dimethoxyphenyl)methyl]-5-[2-(1H-indol-3-yl)ethyl]-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]piperazine-2-carboxamide	KD	5 nM
N-[(1R)-1-{4-[(2,4-dimethoxyphenyl)methyl]-5-[2-(1H-indol-3-yl)ethyl]-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]piperidine-3-carboxamide	EC50	5.3 nM
N-[(1R)-1-{4-benzyl-5-[2-(1H-indol-3-yl)ethyl]-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]piperidine-4-carboxamide	EC50	5.4 nM
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl N-(3-hydroxypropyl)carbamate	EC50	5.5 nM
(2S)-N-[(1R)-1-{4-[(2,4-dimethoxyphenyl)methyl]-5-[2-(1H-indol-3-yl)ethyl]-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]pyrrolidine-2-carboxamide	IC50	5.6 nM
5-(3-bromo-4-{[(4-methanesulfonylphenyl)methyl]amino}phenyl)-6-ethylpyrimidine-2,4-diamine	IC50	5.7 nM
(2S)-N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-4H-1,2,4-triazol-3-yl}ethyl]pyrrolidine-2-carboxamide	KD	6 nM
N-[(1R)-2-(1H-indol-3-yl)-1-{4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-4H-1,2,4-triazol-3-yl}ethyl]oxane-4-carboxamide	IC50	6 nM
6-[(benzyloxy)methyl]-5-(4-{[(5-chlorothiophen-3-yl)methyl]amino}phenyl)pyrimidine-2,4-diamine	IC50	6.3 nM
6-[(benzyloxy)methyl]-5-{4-[(4-methanesulfonylphenyl)methoxy]phenyl}pyrimidine-2,4-diamine	IC50	6.9 nM
(2R)-N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-4H-1,2,4-triazol-3-yl}ethyl]pyrrolidine-2-carboxamide	KD	7 nM
(3R)-N-[(1R)-2-(1H-indol-3-yl)-1-{4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-4H-1,2,4-triazol-3-yl}ethyl]piperidine-3-carboxamide	IC50	7 nM
3-tert-butyl-1-(4-{2,4-diamino-6-[(benzyloxy)methyl]pyrimidin-5-yl}phenyl)urea	EC50	7 nM
3-(4-{2,4-diamino-6-[(benzyloxy)methyl]pyrimidin-5-yl}phenyl)-1-(2-phenylethyl)urea	EC50	7 nM
N-[(1R)-1-{4-[(4-ethylphenyl)methyl]-5-(2-phenylethyl)-4H-1,2,4-triazol-3-yl}-2-(1H-indol-3-yl)ethyl]piperidine-4-carboxamide	EC50	7.7 nM
6-[(benzyloxy)methyl]-5-(4-{[(4-methoxyphenyl)methyl]amino}phenyl)pyrimidine-2,4-diamine	IC50	7.7 nM
2-{5-[(1S)-1-(2-amino-2-methylpropanamido)-2-(benzyloxy)ethyl]-1H-1,2,3,4-tetrazol-1-yl}ethyl N-[2-(3-hydroxyphenyl)ethyl]carbamate	EC50	7.9 nM
(2R)-N-[(1R)-2-(1H-indol-3-yl)-1-{4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-4H-1,2,4-triazol-3-yl}ethyl]pyrrolidine-2-carboxamide	KD	8 nM
(2R)-N-[(1R)-2-(1H-indol-3-yl)-1-{5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-4H-1,2,4-triazol-3-yl}ethyl]piperidine-2-carboxamide	KD	8 nM

ChEMBL bioactivities

2968 potent at pChembl≥5 of 3058 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL1956993
11.00	Ki	0.01	nM	CHEMBL1956994
10.70	IC50	0.02	nM	CHEMBL178475
10.30	EC50	0.05012	nM	CHEMBL480821
10.30	Ki	0.05	nM	CHEMBL1957010
10.11	IC50	0.078	nM	CHEMBL3319217
10.10	IC50	0.08	nM	CHEMBL501253
10.00	Ki	0.1	nM	CHEMBL3939872
10.00	Ki	0.1	nM	CHEMBL3913855
10.00	Ki	0.1	nM	CHEMBL3961108
10.00	Ki	0.1	nM	CHEMBL3907497
10.00	Ki	0.1	nM	CHEMBL3910300
10.00	Ki	0.1	nM	CHEMBL3893048
10.00	Ki	0.1	nM	CHEMBL3895776
10.00	Ki	0.1	nM	CHEMBL3959816
10.00	Ki	0.1	nM	CHEMBL3898794
10.00	Ki	0.1	nM	CHEMBL3918046
10.00	Ki	0.1	nM	CHEMBL3915269
10.00	Ki	0.1	nM	CHEMBL3969367
10.00	Ki	0.1	nM	CHEMBL1923610
10.00	Ki	0.1	nM	CHEMBL1923609
10.00	Ki	0.1	nM	CHEMBL3920049
10.00	Ki	0.1	nM	CHEMBL3934367
10.00	Ki	0.1	nM	CHEMBL1923625
10.00	Ki	0.1	nM	CHEMBL1923623
10.00	Ki	0.1	nM	CHEMBL3905791
10.00	Ki	0.1	nM	CHEMBL3903118
10.00	Ki	0.1	nM	CHEMBL3940705
10.00	Ki	0.1	nM	CHEMBL3918009
10.00	Ki	0.1	nM	CHEMBL3973513
10.00	Ki	0.1	nM	CHEMBL1923626
10.00	Ki	0.1	nM	CHEMBL3935670
10.00	Ki	0.1	nM	CHEMBL3907891
10.00	Ki	0.1	nM	CHEMBL1923642
10.00	Ki	0.1	nM	CHEMBL3922056
10.00	Ki	0.1	nM	CHEMBL3984338
10.00	Ki	0.1	nM	CHEMBL1923637
10.00	Ki	0.1	nM	CHEMBL3914259
10.00	Ki	0.1	nM	CHEMBL3955437
10.00	Ki	0.1	nM	CHEMBL3955179
10.00	Ki	0.1	nM	CHEMBL3929593
10.00	EC50	0.1	nM	CHEMBL4172656
10.00	Ki	0.1	nM	CHEMBL1957001
9.92	IC50	0.12	nM	CHEMBL3218645
9.92	IC50	0.12	nM	CHEMBL2310891
9.92	IC50	0.12	nM	CHEMBL525994
9.85	IC50	0.14	nM	GHRELIN
9.85	Kd	0.14	nM	IBUTAMOREN
9.84	EC50	0.145	nM	CHEMBL4641513
9.82	IC50	0.15	nM	CHEMBL3319221

PubChem BioAssay actives

2493 with measured affinity, of 5292 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
(3S)-3-(2,4-dichlorophenyl)-1-[2-(diethylamino)ethyl]-3-hydroxy-2-oxo-4-(trifluoromethyl)indole-6-carboxamide	242565: Inhibition of [125I]ghrelin binding to human recombinant ghrelin receptor membrane preparation	ic50	<0.0001	uM
6-(1,3-benzothiazol-6-yloxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pyrido[3,2-d]pyrimidin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	<0.0001	uM
6-(4-bromo-2-fluorophenoxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pyrido[3,2-d]pyrimidin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	<0.0001	uM
5-methyl-N-[(1S,2S)-1-[[(3S)-1-methylpiperidin-3-yl]carbamoyl]-2,3-dihydro-1H-inden-2-yl]-1H-indole-2-carboxamide	1505553: Agonist activity at human GHS receptor assessed as intracellular myo-IP1 secretion after 90 mins by HTRF analysis	ec50	0.0001	uM
N-[(3S,4S)-1-(2-chlorophenyl)sulfonyl-3-[[(3S)-1-methylpiperidin-3-yl]carbamoyl]piperidin-4-yl]-5-methyl-1H-indole-2-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0001	uM
Ibutamoren	75335: Compound was evaluated for binding affinity using [35S]MK-0677 (800-1100 Ci/mmol), as radioligand having specific high activity	kd	0.0001	uM
2-chloro-5-ethyl-N-[[6-[3-(4-methylpiperazin-1-yl)propylsulfonyl]-1,3-benzothiazol-2-yl]carbamoyl]benzamide	1181082: Displacement of [125I]human ghrelin from human GHS-R1a expressed in HEK cell membranes after 60 mins by gamma counting method	ic50	0.0001	uM
[(3R)-3-aminopyrrolidin-1-yl]-[(2S)-1-[3-fluoro-4-(5-methylfuran-2-yl)phenyl]sulfonylpiperidin-2-yl]methanone	367942: Agonist activity at human ghrelin receptor by cell based BACMAM FLIPR assay	ec50	0.0001	uM
(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]acetyl]amino]-3-octanoyloxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carboxylic acid	242565: Inhibition of [125I]ghrelin binding to human recombinant ghrelin receptor membrane preparation	ic50	0.0001	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-[2-(1-adamantyl)acetyl]oxy-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75340: Binding affinity to cloned human growth hormone secretagogue receptor type 1 in a competitive binding assay with [35S]MK-0677 as a radiolabeled ligand	ic50	0.0001	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-(8-bromooctanoyloxy)propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75340: Binding affinity to cloned human growth hormone secretagogue receptor type 1 in a competitive binding assay with [35S]MK-0677 as a radiolabeled ligand	ic50	0.0001	uM
6-(1,3-benzothiazol-6-yloxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pyrido[3,4-d]pyrimidin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	0.0001	uM
6-(4-bromo-2-fluorophenoxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pteridin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	0.0001	uM
2-chloro-N-[[6-[3-(4-methylpiperazin-1-yl)propylsulfonyl]-1,3-benzothiazol-2-yl]carbamoyl]-5-pyrrol-1-ylbenzamide	1181082: Displacement of [125I]human ghrelin from human GHS-R1a expressed in HEK cell membranes after 60 mins by gamma counting method	ic50	0.0001	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-undecanoyloxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-1-carboxy-4-(diaminomethylideneamino)butyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75340: Binding affinity to cloned human growth hormone secretagogue receptor type 1 in a competitive binding assay with [35S]MK-0677 as a radiolabeled ligand	ic50	0.0001	uM
5-[4-[(4-nitrophenyl)methylamino]phenyl]-6-(phenylmethoxymethyl)pyrimidine-2,4-diamine	1797847: Receptor Binding Studies and GHS-R Ca2+ Flux Assay from Article 10.1021/jm0510934: “2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists.”	ic50	0.0002	uM
2-chloro-4-cyano-N-[[6-[3-(4-methylpiperazin-1-yl)propylsulfonyl]-1,3-benzothiazol-2-yl]carbamoyl]-5-pyrrolidin-1-ylbenzamide	1181082: Displacement of [125I]human ghrelin from human GHS-R1a expressed in HEK cell membranes after 60 mins by gamma counting method	ic50	0.0002	uM
N-[[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-2-(2,3-dihydro-1-benzofuran-6-ylmethylamino)-5-[(1S,5R)-8-propan-2-yl-8-azabicyclo[3.2.1]oct-2-en-3-yl]pyridine-3-carboxamide	1231858: Binding affinity to ghrelin receptor (unknown origin)	ic50	0.0002	uM
N-[(3S,4S)-1-(2-chlorophenyl)sulfonyl-3-[[(3S)-piperidin-3-yl]carbamoyl]piperidin-4-yl]-5-methyl-1H-indole-2-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0002	uM
N-[(3R,4S)-1-(benzenesulfonyl)-4-[[(2S)-1-methylpyrrolidin-2-yl]methylcarbamoyl]pyrrolidin-3-yl]-5-methyl-1H-indole-2-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0002	uM
N-[(3R,4S)-1-(benzenesulfonyl)-4-[[(3S)-piperidin-3-yl]carbamoyl]pyrrolidin-3-yl]-5-(2,4-dichlorophenyl)-1,2-oxazole-3-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0002	uM
6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-5-methoxy-1-(5-pyridin-2-ylthiophen-2-yl)sulfonyl-2,3-dihydroindole	310590: Agonist activity at GSHR by FLIPR assay	ec50	0.0002	uM
(4S)-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-amino-2-oxoethyl)amino]-3-hydroxypropanoyl]amino]-3-octanoyloxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid	2006564: Displacement of [35S]MK-0677 from human GHSR1a expressed in HEK293 cell membrane by filter binding assay	ic50	0.0002	uM
2-amino-N-[(1S)-1-[1-[4-[2-(2-hydroxyethylsulfonyl)ethylamino]-4-oxobutyl]tetrazol-5-yl]-2-phenylmethoxyethyl]-2-methylpropanamide	329787: Agonist activity at human GHS receptor expressed in H4 cells by FLIPR assay	ec50	0.0002	uM
N-[6-[[2-[1’-[(2R)-2-[(2-amino-2-methylpropanoyl)amino]-3-phenylmethoxypropanoyl]spiro[2H-indole-3,4’-piperidine]-1-yl]sulfonylacetyl]amino]hexyl]-5-[(4S)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanamide	75334: Inhibitory concentration (biotinylated probe) is evaluated for [35S]- MK-0677 binding	ic50	0.0002	uM
(3S)-3-(2,5-dichlorophenyl)-1-[2-(diethylamino)ethyl]-3-hydroxy-2-oxo-4-(trifluoromethyl)indole-6-carboxamide	242565: Inhibition of [125I]ghrelin binding to human recombinant ghrelin receptor membrane preparation	ic50	0.0002	uM
6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-5-methoxy-1-(4-pyridin-2-ylphenyl)sulfonyl-2,3-dihydroindole	310590: Agonist activity at GSHR by FLIPR assay	ec50	0.0002	uM
2-amino-N-[(1S)-1-[1-[4-[2-(3-hydroxyphenyl)ethylamino]-4-oxobutyl]tetrazol-5-yl]-2-phenylmethoxyethyl]-2-methylpropanamide	329787: Agonist activity at human GHS receptor expressed in H4 cells by FLIPR assay	ec50	0.0002	uM
2-amino-N-[(1S)-1-[1-[4-[2-(2-hydroxyethylsulfanyl)ethylamino]-4-oxobutyl]tetrazol-5-yl]-2-phenylmethoxyethyl]-2-methylpropanamide	329787: Agonist activity at human GHS receptor expressed in H4 cells by FLIPR assay	ec50	0.0002	uM
[(3S)-3-aminopyrrolidin-1-yl]-[(2S)-1-[3-fluoro-4-(5-methylfuran-2-yl)phenyl]sulfonylpiperidin-2-yl]methanone	367942: Agonist activity at human ghrelin receptor by cell based BACMAM FLIPR assay	ec50	0.0002	uM
[(3R)-3-aminopyrrolidin-1-yl]-[(2S,3S)-1-[3-fluoro-4-(5-methylfuran-2-yl)phenyl]sulfonyl-3-hydroxypyrrolidin-2-yl]methanone	367942: Agonist activity at human ghrelin receptor by cell based BACMAM FLIPR assay	ec50	0.0002	uM
6-(4-chloro-2-fluorophenoxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pyrido[3,2-d]pyrimidin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	0.0002	uM
6-(4-bromo-2-fluorophenoxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pyrido[2,3-d]pyrimidin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	0.0002	uM
6-(4-chloro-2-fluorophenoxy)-2-methyl-3-[[(3S)-1-propan-2-ylpiperidin-3-yl]methyl]pyrido[3,4-d]pyrimidin-4-one	648794: Displacement of [125I]-Ghrelin from human GHSR membranes overexpressing GSH-R1a by scintillation counting	ki	0.0002	uM
(2R)-N-(1-benzylpiperidin-4-yl)-2-[7-(4-fluoro-2-methylphenoxy)-2,5-dioxo-1,3-dihydro-1,4-benzodiazepin-4-yl]-3-methylbutanamide	654902: Antagonist activity at human GHSR1a receptor assessed as intracellular Ca2+ concentration by aequorin luminescent assay	ic50	0.0002	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-octanoyloxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75340: Binding affinity to cloned human growth hormone secretagogue receptor type 1 in a competitive binding assay with [35S]MK-0677 as a radiolabeled ligand	ic50	0.0002	uM
5-[4-[(4-methylsulfonylphenyl)methylamino]phenyl]-6-(phenylmethoxymethyl)pyrimidine-2,4-diamine	1797847: Receptor Binding Studies and GHS-R Ca2+ Flux Assay from Article 10.1021/jm0510934: “2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists.”	ic50	0.0003	uM
5-[(1S,5R)-6-acetyl-6-azabicyclo[3.2.2]non-2-en-3-yl]-2-(1,3-benzodioxol-5-ylmethylamino)-N-[(3-chloro-4-methoxyphenyl)methyl]pyridine-3-carboxamide	1234912: Displacement of [125I]human ghrelin from human ghrelin receptor expressed in CHO cell membranes incubated for 30 mins by scintillation counting method	ic50	0.0003	uM
N-[(3R,4S)-1-(benzenesulfonyl)-4-[[(3R)-1-methylpiperidin-3-yl]carbamoyl]pyrrolidin-3-yl]-5-methyl-1H-indole-2-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0003	uM
N-[(3R,4S)-1-(benzenesulfonyl)-4-[[(3S)-1-methylpiperidin-3-yl]carbamoyl]pyrrolidin-3-yl]-5-(2-chlorophenyl)-1,2-oxazole-3-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0003	uM
N-[(3R,4S)-1-(benzenesulfonyl)-4-[[(3S)-piperidin-3-yl]carbamoyl]pyrrolidin-3-yl]-5-methyl-1H-indole-2-carboxamide	1665151: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay	ec50	0.0003	uM
N-[(1R)-2-(1H-indol-3-yl)-1-[5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]ethyl]piperidine-4-carboxamide	1797843: Receptor Binding Studies from Article 10.1021/jm0704550: “Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations.”	ic50	0.0003	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-hydroxypropanoyl]amino]-3-octanoyloxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	75340: Binding affinity to cloned human growth hormone secretagogue receptor type 1 in a competitive binding assay with [35S]MK-0677 as a radiolabeled ligand	ic50	0.0003	uM
(4S)-5-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-4-carbamimidamido-1-carboxybutyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-amino-2-oxoethyl)amino]-3-hydroxypropanoyl]amino]-3-octanoyloxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid	2006564: Displacement of [35S]MK-0677 from human GHSR1a expressed in HEK293 cell membrane by filter binding assay	ic50	0.0003	uM
2-[5-[(1R)-1-[(2-amino-2-methylpropanoyl)amino]-4,4-difluoro-4-phenylbutyl]tetrazol-1-yl]ethyl N-(4-hydroxybutyl)carbamate	343588: Agonist activity at GHS receptor	ec50	0.0003	uM
2-chloro-5-ethoxy-N-[[6-[3-(4-methylpiperazin-1-yl)propylsulfonyl]-1,3-benzothiazol-2-yl]carbamoyl]benzamide	1181082: Displacement of [125I]human ghrelin from human GHS-R1a expressed in HEK cell membranes after 60 mins by gamma counting method	ic50	0.0003	uM
N-[(2R)-1-(3a-benzyl-2-tert-butyl-3-oxo-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl)-3-[(3,4-difluorophenyl)methoxy]-1-oxopropan-2-yl]-2-amino-2-methylpropanamide	92297: In vitro binding affinity against human type 1a growth hormone secretagogue receptor (hGHS-R1a), using [125I]ghrelin as radioligand.	ki	0.0003	uM
N-[(2R)-1-[[(2R)-1-[[(1S)-2-amino-2-oxo-1-phenylethyl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]piperidine-4-carboxamide	306735: Agonist activity at human GHS-R1	ec50	0.0003	uM
2-[5-[(1S)-1-[(2-amino-2-methylpropanoyl)amino]-2-[(2-phenylphenyl)methoxy]ethyl]tetrazol-1-yl]ethyl N-(4-hydroxybutyl)carbamate	314834: Inhibition of human growth hormone secretagogue receptor assessed as measuring intracellular calcium level by FLIPR assay	ec50	0.0003	uM
2-amino-N-[(1S)-1-[1-[(2R)-1-cyano-3-(2-hydroxyphenoxy)propan-2-yl]tetrazol-5-yl]-2-phenylmethoxyethyl]-2-methylpropanamide	315822: Agonist activity at human GHS receptor expressed in H4 glioma cells assessed as intracellular calcium concentration by FLIPR assay	ec50	0.0003	uM

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
arctigenin	increases reaction, decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
ulimorelin	affects binding, increases activity	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carmustine	decreases expression	1
Glucose	increases expression, increases reaction, decreases reaction	1
Aflatoxin B1	decreases methylation	1
Azithromycin	increases expression	1

ChEMBL screening assays

373 unique, capped per target: 238 functional, 135 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001323	Functional	Inverse agonist activity at human ghrelin receptor Arg6:20Gln(Arg283) mutant expressed in african green monkey COS7 cells assessed as inhibition of constitutively stimulated inositol phosphate accumulation relative to wild type	Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. — J Biol Chem
CHEMBL1007236	Binding	Displacement of [35S]MK677 from human ghrelin receptor expressed in african green monkey COS7 cells relative to [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P peptide	Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. — J Biol Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D1WJ	Abcam A-549 GHSR KO	Cancer cell line	Male
CVCL_D2AY	Abcam HCT 116 GHSR KO	Cancer cell line	Male
CVCL_H436	CHO-K1/GHSR	Spontaneously immortalized cell line	Female
CVCL_KX13	PathHunter CHO-K1 GHSR1b beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA34	PathHunter U2OS GHSR1a beta-arrestin-1	Cancer cell line	Female
CVCL_ZK27	T-REx Tango GHSR-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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