Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX5FZDJ)

• DOT Name: Orexigenic neuropeptide QRFP (QRFP)
• Synonyms: P518
• Gene Name: QRFP
• Related Disease:
  Hyperinsulinemia
  Alzheimer disease
  Analgesia
  Hyperglycemia
  Narcolepsy
• UniProt ID: OX26_HUMAN
• Pfam ID: PF11109
• Sequence:
  MVRPYPLIYFLFLPLGACFPLLDRREPTDAMGGLGAGERWADLAMGPRPHSVWGSSRWLR
  ASQPQALLVIARGLQTSGREHAGCRFRFGRQDEGSEATGFLPAAGEKTSGPLGNLAEELN
  GYSRKKGGFSFRFGRR
• Function: Stimulates feeding behavior, metabolic rate and locomotor activity and increases blood pressure. May have orexigenic activity. May promote aldosterone secretion by the adrenal gland.
• Tissue Specificity: Expressed widely in the brain with highest expression levels in the cerebellum, medulla, pituitary, retina, vestibular nucleus, and white matter. Also expressed in the bladder, colon, coronary artery, parathyroid gland, prostate, 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
Hyperinsulinemia	DISIDWT6	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Analgesia	DISK3TVI	Strong	Biomarker	[3]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[1]
Narcolepsy	DISLCNLI	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Orexigenic neuropeptide QRFP (QRFP).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Orexigenic neuropeptide QRFP (QRFP).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Orexigenic neuropeptide QRFP (QRFP).	[6]

References

• [1] 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.
• [2] 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.
• [3] Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors.Neuropharmacology. 2013 Dec;75:164-71. doi: 10.1016/j.neuropharm.2013.07.012. Epub 2013 Aug 2.
• [4] Molecular codes and in vitro generation of hypocretin and melanin concentrating hormone neurons.Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):17061-17070. doi: 10.1073/pnas.1902148116. Epub 2019 Aug 2.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.