Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT31N14I)

• DOT Name: Pyroglutamylated RF-amide peptide receptor (QRFPR)
• Synonyms: AQ27; G-protein coupled receptor 103; Orexigenic neuropeptide QRFP receptor; SP9155
• Gene Name: QRFPR
• Related Disease:
  Alzheimer disease
  Benign prostatic hyperplasia
  Hyperglycemia
  Prostate cancer
  Prostate carcinoma
• UniProt ID: QRFPR_HUMAN
• Pfam ID: PF00001
• Sequence:
  MQALNITPEQFSRLLRDHNLTREQFIALYRLRPLVYTPELPGRAKLALVLTGVLIFALAL
  FGNALVFYVVTRSKAMRTVTNIFICSLALSDLLITFFCIPVTMLQNISDNWLGGAFICKM
  VPFVQSTAVVTEILTMTCIAVERHQGLVHPFKMKWQYTNRRAFTMLGVVWLVAVIVGSPM
  WHVQQLEIKYDFLYEKEHICCLEEWTSPVHQKIYTTFILVILFLLPLMVMLILYSKIGYE
  LWIKKRVGDGSVLRTIHGKEMSKIARKKKRAVIMMVTVVALFAVCWAPFHVVHMMIEYSN
  FEKEYDDVTIKMIFAIVQIIGFSNSICNPIVYAFMNENFKKNVLSAVCYCIVNKTFSPAQ
  RHGNSGITMMRKKAKFSLRENPVEETKGEAFSDGNIEVKLCEQTEEKKKLKRHLALFRSE
  LAENSPLDSGH
• Function: Receptor for the orexigenic neuropeptide QRFP. The activity of this receptor is mediated by G proteins that modulate adenylate cyclase activity and intracellular calcium levels.
• Tissue Specificity: Expressed widely in the brain with high levels in the hypothalamus, trigeminal ganglia and vestibular neurons, and moderate levels in the amygdala, cortex, pituitary, hippocampus, thalamus, caudate nucleus and medulla oblongata. In peripheral tissues, expressed at high levels in the retina and at moderate levels in the heart, kidney, testis and thyroid.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Orexin and neuropeptides FF and QRFP bind to their respective receptors (R-HSA-389397)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[2]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Pyroglutamylated RF-amide peptide receptor (QRFPR).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Pyroglutamylated RF-amide peptide receptor (QRFPR).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Pyroglutamylated RF-amide peptide receptor (QRFPR).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Pyroglutamylated RF-amide peptide receptor (QRFPR).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Pyroglutamylated RF-amide peptide receptor (QRFPR).	[9]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Pyroglutamylated RF-amide peptide receptor (QRFPR).	[8]

References

• [1] Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103.Sci Rep. 2015 Jul 30;5:12584. doi: 10.1038/srep12584.
• [2] Involvement of the glutamine RFamide peptide and its cognate receptor GPR103 in prostate cancer.Oncol Rep. 2019 Feb;41(2):1140-1150. doi: 10.3892/or.2018.6893. Epub 2018 Nov 27.
• [3] Neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice.Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):E147-E157. doi: 10.1152/ajpendo.00540.2018. Epub 2019 May 14.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.