PROKR1

Summary

PROKR1 (prokineticin receptor 1, HGNC:4524) is a protein-coding gene on chromosome 2p13.3, encoding Prokineticin receptor 1 (Q8TCW9). Receptor for prokineticin 1.

This gene encodes a member of the G-protein-coupled receptor family. The encoded protein binds to prokineticins (1 and 2), leading to the activation of MAPK and STAT signaling pathways. Prokineticins are protein ligands involved in angiogenesis and inflammation. The encoded protein is expressed in peripheral tissues such as those comprising the circulatory system, lungs, reproductive system, endocrine system and the gastrointestinal system. The protein may be involved in signaling in human fetal ovary during initiation of primordial follicle formation. Sequence variants in this gene may be associated with recurrent miscarriage.

Source: NCBI Gene 10887 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_138964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4524
Approved symbol	PROKR1
Name	prokineticin receptor 1
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PKR1, ZAQ, GPR73a
Ensembl gene	ENSG00000169618
Ensembl biotype	protein_coding
OMIM	607122
Entrez	10887

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000303786

RefSeq mRNA: 1 — MANE Select: NM_138964 NM_138964

CCDS: CCDS1889

Canonical transcript exons

ENST00000303786 — 3 exons

Exon	Start	End
ENSE00001518145	68645662	68646306
ENSE00001581622	68643579	68643848
ENSE00003763304	68654880	68658251

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 93.27.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.89	gold quality
ganglionic eminence	UBERON:0004023	72.67	gold quality
omental fat pad	UBERON:0010414	52.12	gold quality
cortical plate	UBERON:0005343	50.95	silver quality
colonic epithelium	UBERON:0000397	49.81	gold quality
vermiform appendix	UBERON:0001154	48.20	gold quality
pituitary gland	UBERON:0000007	46.14	gold quality
adipose tissue	UBERON:0001013	45.10	gold quality
thoracic mammary gland	UBERON:0005200	45.08	gold quality
adenohypophysis	UBERON:0002196	44.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	43.64	gold quality
skeletal muscle tissue	UBERON:0001134	40.76	gold quality
right adrenal gland	UBERON:0001233	40.62	gold quality
granulocyte	CL:0000094	40.34	gold quality
hypothalamus	UBERON:0001898	40.26	gold quality
colon	UBERON:0001155	40.20	gold quality
ventricular zone	UBERON:0003053	40.04	gold quality
placenta	UBERON:0001987	39.89	silver quality
tonsil	UBERON:0002372	39.78	gold quality
rectum	UBERON:0001052	39.62	silver quality
stromal cell of endometrium	CL:0002255	39.02	gold quality
saliva-secreting gland	UBERON:0001044	38.93	silver quality
endometrium	UBERON:0001295	38.74	gold quality
lower esophagus mucosa	UBERON:0035834	38.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	38.70	gold quality
intestine	UBERON:0000160	38.35	silver quality
muscle tissue	UBERON:0002385	38.32	silver quality
bone marrow cell	CL:0002092	38.21	gold quality
adrenal gland	UBERON:0002369	37.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

Literature-anchored findings (GeneRIF, showing 23)

• molecular cloning, amino acid sequence and expression in several human tissues (PMID:12427552)
• Paracrine role for the PKs and their receptors in endometrial vascular function. (PMID:15126578)
• study demonstrated that prokineticin 1 and 2 and their receptors are expressed in human prostate and that their levels increased with prostate malignancy (PMID:16763065)
• PROK1 and PROKR1 expression is elevated in human decidua during early pregnancy PROK1-PROKR1 interaction regulates expression of a host of implantation-related genes. (PMID:18339712)
• Data shown that PROK1-PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua. (PMID:19801577)
• The functional characteristics of coronary endothelial cells depend on the expression of PKR1 and PKR2 levels and the divergent signaling pathways used by these receptors. (PMID:20023120)
• Data show that expression of PK1 and PKR1 was detected in primary MM cells and myeloma cell lines. (PMID:20795791)
• Two tag SNPs of PKR1 (rs4627609, rs6731838) were significantly associated with idiopathic recurrent pregnancy loss. (PMID:20847187)
• Data suggest that smoking targets human Fallopian tubes via nAChRalpha-7 to increase tubal PROKR1, leading to alterations in the tubal microenvironment that could predispose to ectopic pregnancy. (PMID:20864676)
• Findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in combination with RET or GDNF mutations, provide evidence to consider them as susceptibility genes for HSCR. (PMID:21858136)
• The number of PKR1 is not reduced in preeclampsia. (PMID:21876489)
• The results suggest an identical transmembrane-bundle binding site for hPKR1 and hPKR2. (PMID:22132188)
• hCG increases EG-VEGF, PROKR1 and PROKR2 mRNA and protein expression in a dose- and time-dependent manner, demonstrating a new role for hCG in the regulation of EG-VEGF and its receptors (PMID:22138749)
• I397V variant confers lower risk for recurrent miscarriage (PMID:23687280)
• Study corroborates the clinical relevance of the EG-VEGF system in human early pregnancy, and provides evidence for the gene-gene interactions of EG-VEGF and PROKR variants. (PMID:25064403)
• Expression of PROK1 and PROKR1 was significantly higher in mid-gestation ovaries (17-20 wk) than at earlier gestations (8-11 and 14-16 wk). (PMID:26192875)
• EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease. (PMID:26475302)
• Data suggest that prokineticins (PROK1 and PROK2) and prokineticin receptors (PROKR1 and PROKR2) act as main regulators of physiological functions of ovary, uterus, placenta, and testis. [REVIEW] (PMID:26574895)
• a significant association between PKR2 rs6053283 polymorphism and Recurrent pregnancy loss (RPL)(P=0.003), whereas no association was observed between PKR1 rs4627609 polymorphism and RPL (P=0.929) in the Chinese Han population. (PMID:26984842)
• PROK-1 and its receptors are involved in the pathogenesis and development of endometriosis (PMID:31304922)
• The role of prokineticins in recurrent implantation failure. (PMID:32585394)
• Prokineticin receptor 1 ameliorates insulin resistance in skeletal muscle. (PMID:33184929)
• Prokineticin receptors interact unselectively with several G protein subtypes but bind selectively to beta-arrestin 2. (PMID:33811988)

Cross-species orthologs

0 orthologs

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR88 (ENSG00000181656), GPR19 (ENSG00000183150), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

Prokineticin receptor 1 — Q8TCW9 (reviewed: Q8TCW9)

Alternative names: G-protein coupled receptor 73, G-protein coupled receptor ZAQ, GPR73a

All UniProt accessions (1): Q8TCW9

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for prokineticin 1. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of p44/p42 mitogen-activated protein kinase. May play a role during early pregnancy.

Subcellular location. Cell membrane.

Tissue specificity. Localizes to glandular epithelium, stroma and vascular endothelial cells of first trimester decidua (at protein level). Up-regulated in first trimester decidua when compared with non-pregnant endometrium. Expressed in the stomach, throughout the small intestine, colon, rectum, thyroid gland, pituitary gland, salivary gland, adrenal gland, testis, ovary, brain, spleen, prostate and pancreas.

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

RefSeq proteins (1): NP_620414* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000611	NPY_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, glycosylation site 3, chain 1, disulfide bond 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCW9-F1	77.64	0.46

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): 137–217

Glycosylation sites (3): 11, 14, 36

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: 65 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MARTINEZ_RB1_TARGETS_DN, AML_Q6, GROSS_HIF1A_TARGETS_DN, GOBP_RESPONSE_TO_HORMONE, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP, OSF2_Q6, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOBP_RHYTHMIC_PROCESS, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), circadian rhythm (GO:0007623), cellular response to hormone stimulus (GO:0032870), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), neuropeptide Y receptor activity (GO:0004983)

GO Cellular Component (2): plasma membrane (GO:0005886), 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
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor activity	1
signal transduction	1
rhythmic process	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	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

592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROKR1	PROK1	P58294	998
PROKR1	PROK2	Q9HC23	994
PROKR1	ADCY3	O60266	767
PROKR1	MRAP2	Q96G30	752
PROKR1	ALDH18A1	P54886	704
PROKR1	GNA11	P29992	653
PROKR1	ADCY8	P40145	651
PROKR1	PSMC4	P43686	636
PROKR1	CDC73	Q6P1J9	514
PROKR1	MC2R	Q01718	510
PROKR1	DNAAF10	Q96MX6	501
PROKR1	PPP3R1	P06705	499
PROKR1	CASR	P41180	499
PROKR1	GNAQ	P50148	495
PROKR1	TRPV1	Q8NER1	487

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RAMP1	PROKR1	psi-mi:“MI:0915”(physical association)	0.400
PROKR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
PROKR1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
PROKR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	PROKR1	psi-mi:“MI:0915”(physical association)	0.400
CFTR	PROKR1	psi-mi:“MI:0915”(physical association)	0.370
PROKR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): PROKR1 (Affinity Capture-MS), TELO2 (Affinity Capture-MS), RARS2 (Affinity Capture-MS), XPO7 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), UCK2 (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), IPO13 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), THADA (Affinity Capture-MS), TTI1 (Affinity Capture-MS), FANCD2 (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), PI4KA (Affinity Capture-MS)

ESM2 similar proteins: O02813, O02835, O02836, O43614, O46639, O62809, O93603, P0C0L6, P21555, P21761, P25929, P30731, P32247, P34981, P34992, P35382, P47751, P49146, P56719, P58308, P70031, P79113, P79217, P79945, P97295, Q04573, Q1RMU8, Q28596, Q56H79, Q5IS62, Q61041, Q61212, Q63447, Q6W5P4, Q8BZP8, Q8K458, Q8NFJ6, Q8R415, Q8SPN1, Q8TCW9

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PROK1	up-regulates	PROKR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

501 predictions. Top by Δscore:

Variant	Effect	Δscore
2:68643803:GAA:G	donor_gain	0.9900
2:68647937:AG:A	donor_gain	0.9900
2:68654875:CCTA:C	acceptor_loss	0.9900
2:68654877:TAGGT:T	acceptor_loss	0.9900
2:68654878:A:G	acceptor_loss	0.9900
2:68646304:CAGG:C	donor_loss	0.9800
2:68646306:GGT:G	donor_loss	0.9800
2:68646307:G:A	donor_loss	0.9800
2:68646308:T:A	donor_loss	0.9800
2:68654872:T:A	acceptor_gain	0.9800
2:68654878:A:AG	acceptor_gain	0.9800
2:68654879:G:GG	acceptor_gain	0.9800
2:68654879:GGT:G	acceptor_gain	0.9800
2:68643844:CGCAG:C	donor_loss	0.9700
2:68643846:CAG:C	donor_loss	0.9700
2:68643847:AG:A	donor_loss	0.9700
2:68643848:GG:G	donor_loss	0.9700
2:68643849:GTACA:G	donor_loss	0.9700
2:68643850:T:C	donor_loss	0.9700
2:68647936:TA:T	donor_gain	0.9700
2:68643980:A:T	donor_gain	0.9600
2:68646307:G:GG	donor_gain	0.9600
2:68645658:AAAG:A	acceptor_gain	0.9400
2:68646302:GACAG:G	donor_gain	0.9300
2:68643965:G:GG	donor_gain	0.9200
2:68654878:AG:A	acceptor_gain	0.9200
2:68654879:GG:G	acceptor_gain	0.9200
2:68654879:GGTAT:G	acceptor_gain	0.9200
2:68657027:G:GC	acceptor_gain	0.9200
2:68645658:A:AG	acceptor_gain	0.8900

AlphaMissense

2605 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:68646211:G:C	W130C	0.999
2:68646211:G:T	W130C	0.999
2:68646209:T:A	W130R	0.997
2:68646209:T:C	W130R	0.997
2:68646230:T:A	C137S	0.997
2:68646231:G:C	C137S	0.997
2:68654953:T:A	W187R	0.997
2:68654953:T:C	W187R	0.997
2:68646231:G:A	C137Y	0.996
2:68646232:C:G	C137W	0.996
2:68655044:G:A	C217Y	0.996
2:68655314:G:C	R307P	0.996
2:68646230:T:C	C137R	0.995
2:68655043:T:C	C217R	0.995
2:68655057:G:C	W221C	0.995
2:68655057:G:T	W221C	0.995
2:68655386:C:A	A331D	0.995
2:68655391:A:C	S333R	0.995
2:68655393:C:A	S333R	0.995
2:68655393:C:G	S333R	0.995
2:68655043:T:A	C217S	0.994
2:68655044:G:C	C217S	0.994
2:68655045:C:G	C217W	0.994
2:68655055:T:A	W221R	0.993
2:68655055:T:C	W221R	0.993
2:68655397:A:C	S335R	0.993
2:68655399:C:A	S335R	0.993
2:68655399:C:G	S335R	0.993
2:68646144:A:C	D108A	0.992
2:68646231:G:T	C137F	0.991

dbSNP variants (sampled 300 via entrez): RS1000008730 (2:68651346 G>C), RS1000112925 (2:68642777 A>G), RS1000240039 (2:68657474 C>T), RS1000433694 (2:68643069 T>C), RS1000697091 (2:68648289 G>A), RS1000702393 (2:68641624 T>C), RS1001369207 (2:68651858 A>G), RS1001422930 (2:68651609 C>T), RS1001643972 (2:68645115 T>C,G), RS1001649723 (2:68657877 A>C,G), RS1001747667 (2:68657132 A>G), RS1001750134 (2:68645671 G>C), RS1001920466 (2:68646487 A>G), RS1001985848 (2:68647085 G>A), RS1001990035 (2:68645377 C>G)

Disease associations

OMIM: gene MIM:607122 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Mondo (2): long QT syndrome (MONDO:0002442), Hirschsprung disease (MONDO:0018309)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5649 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Prokineticin receptors

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
MIT1	Full agonist	8.4	pIC50
prokineticin-2	Full agonist	8.4	pIC50
[125I]BH-MIT1	Agonist	8.39	pIC50
triazine compound PC1	Antagonist	7.66	pKi
prokineticin-1	Full agonist	7.6	pIC50
prokineticin-2β	Full agonist	7.5	pIC50
triazine compound PC7	Antagonist	7.48	pIC50
IS20	Agonist	7.36	pEC50
triazine compound PC10	Antagonist	6.96	pIC50
IS1	Agonist	5.6	pEC50

Binding affinities (BindingDB)

250 measured of 250 human assays (250 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(-)-(2R)-2-Methyl-3- (benzimidazol-4- ylmethylamino)-N-(9-chloro- 3,4-dihydro-2H-1,5- benzodioxepin-7-ylmethyl)-N- isobutylpropanamide	KI	3.5 nM	US-10780095: Compositions and methods for treating disorders of circadian and diurnal rhythms using prokineticin 2 agonists and antagonists
(-)-(2R)-1-(5-fluro- benzimidazol-4-ylmethyl)-N- (9-chloro-3,4-dihydro-2H-1,5- benzodioxepin-7-ylmethyl)-N- isobutylmorpholine-2- carboxamide	KI	6.14 nM	US-10780095: Compositions and methods for treating disorders of circadian and diurnal rhythms using prokineticin 2 agonists and antagonists
3-[2-({5-[(4-ethylphenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,4,5,6-tetrahydro-1,3,5-triazin-2-yl}amino)ethyl]guanidine	KI	22 nM
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine	IC50	30 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine	IC50	30 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
5-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine	IC50	30 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine	IC50	40 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
2-(4-Chlorophenyl)-2-(1-((3,5-dimethyl-1H-pyrazol-4-yl) sulfonyl)piperidin-4-ylidene)acetonitrile	IC50	40 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
2-(4-Chlorophenyl)-2-(1-((1,3,5-trimethyl-1H-pyrazol-4-yl) sulfonyl)piperidin-4-ylidene)acetonitrile	IC50	40 nM	US-10208016: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-[(4-chloro-2-methoxyphenyl)methyl]-1-(1,3,5-trimethylpyrazol-4-yl)sulfonylpiperidine	IC50	50 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridin-2-amine	IC50	50 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridin-2-amine formate	IC50	50 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
2-(4-Chlorophenyl)-2-(1-((3,5-diethyl-1H-pyrazol-4-yl) sulfonyl)piperidin-4-ylidene)acetonitrile	IC50	50 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-[(4-chlorophenyl)-methoxymethyl]-1-(1,3,5-trimethylpyrazol-4-yl)sulfonylpiperidine	IC50	60 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
3-((1-(3,5-Dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene) fluoromethyl)quinoline	IC50	60 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-[(4-chloro-2-methoxyphenyl)methyl]-1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]piperidine	IC50	70 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
3-Chloro-5-{[3-(4-chloro-2-methylphenyl)piperidin-1-yl]carbonyl}pyridazine	IC50	70 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine	IC50	70 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
(-)-(3R)-1-(5-fluro- benzimidazol-4-ylmethyl)-N- (9-chloro-3,4-dihydro-2H-1,5- benzodioxepin-7-ylmethyl)-N- isobutylpyrrolidine-3- carboxamide	KI	71.3 nM	US-10780095: Compositions and methods for treating disorders of circadian and diurnal rhythms using prokineticin 2 agonists and antagonists
5-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridazin-3-amine	IC50	80 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
2-(Azetidin-1-yl)-4-{[3-(4-chloro-2-methylphenyl)piperidin-1-yl]carbonyl}pyridine	IC50	90 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
5-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine	IC50	90 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
3-Chloro-5-{[3-(4-methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}pyridazine	IC50	100 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine	IC50	100 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridin-2-amine	IC50	100 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidine	IC50	100 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
5-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridazin-3-amine	IC50	110 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
3-(4-Chloro-2-methylphenyl)-1-[(1-ethyl-1H-pyrazol-4-yl)carbonyl]piperidine	IC50	110 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
5-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine	IC50	120 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine	IC50	130 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
5-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine	IC50	130 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
5-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridazin-3-amine	IC50	130 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-[(4-chloro-2-methoxyphenyl)methyl]-4-fluoro-1-(1,3,5-trimethylpyrazol-4-yl)sulfonylpiperidine	IC50	140 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-1-methyl-1H-pyrazol-5-amine	IC50	150 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
2-(1-((3,5-Dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)-2-(4-(trifluoromethoxy)phenypacetonitrile	IC50	150 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-[(4-chlorophenyl)-methoxymethyl]-1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]piperidine	IC50	160 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
5-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine	IC50	160 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-((4-Chlorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl) sulfonyl)piperidine	IC50	160 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-(4-chloro-2-methoxyphenoxy)-1-(1,3,5-trimethylpyrazol-4-yl)sulfonylpiperidine	IC50	170 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
4-[(4-chloro-2-methoxyphenyl)methyl]-1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-fluoropiperidine	IC50	170 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
5-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine	IC50	170 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
3-(4-Chloro-2-methylphenyl)-1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidine	IC50	170 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1-ethyl-1H-pyrazol-4-yl)carbonyl]piperidine	IC50	170 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-{[(3R)-3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine	IC50	180 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
3-(4-Chloro-2-methylphenyl)-1-{[1-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidine	IC50	180 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
2-(4-Chloro-2-fluorophenyl)-2-(1-((3,5-dimethyl-1H-pyrazol-4-yl) sulfonyl)piperidin-4-ylidene)acetonitrile	IC50	180 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-{[3-(2,4-Dichlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine	IC50	190 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
N,N-Dimethyl-4-{[3-(2-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine	IC50	190 nM	US-9790201: Piperidine and azepine derivatives as prokineticin receptor modulators
4-((4-Chloro-3-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl) sulfonyl)piperidine	IC50	190 nM	US-10308635: 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
4-(4-chloro-2-methoxyphenoxy)-1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]piperidine	IC50	200 nM	US-9475795: Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases

ChEMBL bioactivities

679 potent at pChembl≥5 of 679 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.72	IC50	19	nM	CHEMBL551383
7.68	IC50	21	nM	CHEMBL562111
7.66	Ki	22	nM	CHEMBL457515
7.66	IC50	22	nM	CHEMBL550780
7.57	IC50	27	nM	CHEMBL551583
7.52	IC50	30	nM	CHEMBL6008371
7.52	IC50	30	nM	CHEMBL5865148
7.52	IC50	30	nM	CHEMBL5793849
7.48	IC50	33	nM	CHEMBL550577
7.40	IC50	40	nM	CHEMBL3889670
7.40	IC50	40	nM	CHEMBL3977908
7.40	IC50	40	nM	CHEMBL6037874
7.33	IC50	47	nM	CHEMBL549558
7.30	IC50	50	nM	CHEMBL3917980
7.30	IC50	50	nM	CHEMBL3956849
7.30	IC50	50	nM	CHEMBL5982665
7.30	IC50	50	nM	CHEMBL5915456
7.29	IC50	51	nM	CHEMBL559719
7.22	IC50	60	nM	CHEMBL3898347
7.22	IC50	60	nM	CHEMBL3893095
7.16	IC50	70	nM	CHEMBL3947348
7.16	IC50	70	nM	CHEMBL5885972
7.16	IC50	70	nM	CHEMBL5915764
7.16	IC50	70	nM	CHEMBL5793849
7.10	IC50	80	nM	CHEMBL3986275
7.10	IC50	80	nM	CHEMBL5868710
7.05	IC50	90	nM	CHEMBL6000858
7.05	IC50	90	nM	CHEMBL5986179
7.00	IC50	100	nM	CHEMBL5847945
7.00	IC50	100	nM	CHEMBL5755600
7.00	IC50	100	nM	CHEMBL5985423
7.00	IC50	100	nM	CHEMBL6034407
6.96	IC50	110	nM	CHEMBL6026169
6.96	IC50	110	nM	CHEMBL5824718
6.92	IC50	120	nM	CHEMBL5936968
6.89	IC50	130	nM	CHEMBL5873039
6.89	IC50	130	nM	CHEMBL5875922
6.89	IC50	130	nM	CHEMBL5919895
6.85	IC50	140	nM	CHEMBL3898520
6.82	IC50	150	nM	CHEMBL3953005
6.82	IC50	150	nM	CHEMBL5912868
6.80	IC50	160	nM	CHEMBL3919323
6.80	IC50	160	nM	CHEMBL3986275
6.80	IC50	160	nM	CHEMBL5869152
6.77	IC50	170	nM	CHEMBL3897887
6.77	IC50	170	nM	CHEMBL3958623
6.77	IC50	170	nM	CHEMBL6052437
6.77	IC50	170	nM	CHEMBL5855521
6.77	IC50	170	nM	CHEMBL5897902
6.75	IC50	180	nM	CHEMBL3928918

PubChem BioAssay actives

33 with measured affinity, of 43 total; 30 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
2-[2-[[5-[(4-chlorophenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0190	uM
2-[2-[[1,5-bis[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0210	uM
2-[2-[[5-[(4-ethylphenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	1798670: Receptor Binding Assay from Article 10.1021/jm800854e: “Triazine Compounds as Antagonists at Bv8-Prokineticin Receptors.”	ki	0.0220	uM
2-[2-[[5-[(3,4-dichlorophenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0220	uM
2-[2-[[1-[(4-hydroxyphenyl)methyl]-5-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0270	uM
2-[2-[[5-[(4-fluorophenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0330	uM
2-[2-[[5-[(3,4-dichlorophenyl)methyl]-1-[[4-(difluoromethoxy)phenyl]methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0470	uM
2-[2-[[5-[(4-methoxyphenyl)methyl]-1-[(6-methoxy-3-pyridinyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.0510	uM
[3-(5-chloro-3-methyl-2-pyridinyl)-3-fluoropiperidin-1-yl]-[2-(methylamino)-4-pyridinyl]methanone	1249733: Antagonist activity at human PKR1 expressed in rat RBL2H3 cells assessed as inhibition of PK1-stimulated intracellular calcium release incubated for 10 mins prior to PK1 stimulation by FLIPR assay	ic50	0.2900	uM
2-[2-[[5-[(4-cyanophenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.3180	uM
[2-(dimethylamino)-4-pyridinyl]-[3-(1-propan-2-ylbenzimidazol-2-yl)piperidin-1-yl]methanone	1249733: Antagonist activity at human PKR1 expressed in rat RBL2H3 cells assessed as inhibition of PK1-stimulated intracellular calcium release incubated for 10 mins prior to PK1 stimulation by FLIPR assay	ic50	0.3200	uM
(1-ethylpyrazol-4-yl)-[3-(1-propan-2-ylindol-2-yl)piperidin-1-yl]methanone	1249733: Antagonist activity at human PKR1 expressed in rat RBL2H3 cells assessed as inhibition of PK1-stimulated intracellular calcium release incubated for 10 mins prior to PK1 stimulation by FLIPR assay	ic50	0.3300	uM
2-[2-[[5-benzyl-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.3360	uM
6-(2-aminoethylamino)-3-[(4-ethylphenyl)methyl]-1-[(4-methoxyphenyl)methyl]-1,3,5-triazine-2,4-dione	1798670: Receptor Binding Assay from Article 10.1021/jm800854e: “Triazine Compounds as Antagonists at Bv8-Prokineticin Receptors.”	ki	0.4400	uM
2-[2-[[5-[2-(4-methoxyphenyl)ethyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.4610	uM
2-[2-[[5-[(3,4-dichlorophenyl)methyl]-4,6-dioxo-1-[(4-propoxyphenyl)methyl]-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	0.5150	uM
(3-amino-1-methylpyrazol-4-yl)-[3-(5-chloro-1-ethylindol-2-yl)piperidin-1-yl]methanone	1249733: Antagonist activity at human PKR1 expressed in rat RBL2H3 cells assessed as inhibition of PK1-stimulated intracellular calcium release incubated for 10 mins prior to PK1 stimulation by FLIPR assay	ic50	0.9100	uM
2-[2-[[5-[(4-hydroxyphenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	1.1600	uM
2-[3-[[5-[(3,4-dichlorophenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]propyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	1.2100	uM
2-[2-[[5-[(4-chlorophenyl)methyl]-1-(furan-3-yl)-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	1.8700	uM
2-[2-[[5-butyl-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	2.1800	uM
2-[2-[[1-[(4-methoxyphenyl)methyl]-4,6-dioxo-5-(2-phenylethyl)-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	2.5000	uM
2-[2-[[5-(furan-2-yl)-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	2.5900	uM
2-[2-[[5-[(4-fluorophenyl)methyl]-1-[2-(4-methoxyphenyl)ethyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	2.8600	uM
2-[2-[[1-[(4-methoxycyclohexyl)methyl]-5-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	3.2600	uM
2-[2-[[5-[(3-methoxyphenyl)methyl]-1-[(4-methoxyphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	3.6900	uM
6-[2-(4,5-dihydro-1H-imidazol-2-ylamino)ethylamino]-3-[(4-ethylphenyl)methyl]-1-[(4-methoxyphenyl)methyl]-1,3,5-triazine-2,4-dione	1798670: Receptor Binding Assay from Article 10.1021/jm800854e: “Triazine Compounds as Antagonists at Bv8-Prokineticin Receptors.”	ki	4.7190	uM
2-[2-[[1-benzyl-5-[(4-chlorophenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	4.7800	uM
2-[2-[[5-[(3,4-dichlorophenyl)methyl]-1-hexyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]ethyl]guanidine	424455: Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	ic50	6.5100	uM
[6-(methylamino)pyridazin-4-yl]-[3-(3-methyl-1H-indol-2-yl)piperidin-1-yl]methanone	1249733: Antagonist activity at human PKR1 expressed in rat RBL2H3 cells assessed as inhibition of PK1-stimulated intracellular calcium release incubated for 10 mins prior to PK1 stimulation by FLIPR assay	ic50	7.4100	uM

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

ChEMBL screening assays

19 unique, capped per target: 11 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1057723	Functional	Antagonist activity at human PKR1 expressed in HEK293 cells assessed as inhibition of PK1-induced calcium mobilization by FLIPR assay	Triazinediones as prokineticin 1 receptor antagonists. Part 1: SAR, synthesis and biological evaluation. — Bioorg Med Chem Lett
CHEMBL3889151	Binding	Biological Assay: Prokineticin receptor 1 (PKR1) antagonists may be functionally assessed by measurement of change in intracellular calcium levels induced by Gq mediated increase in inositol triphosphate (IP3) levels. The ability of a compo	Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV65	cAMP Hunter CHO-K1 PROKR1 Gs	Spontaneously immortalized cell line	Female
CVCL_KY84	PathHunter CHO-K1 PROKR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB15	PathHunter U2OS PROKR1 Total GPCR Internalization	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval