Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSN4PCR)

• DOT Name: Nociceptin receptor (OPRL1)
• Synonyms: Kappa-type 3 opioid receptor; KOR-3; Orphanin FQ receptor
• Gene Name: OPRL1
• UniProt ID: OPRX_HUMAN
• PDB ID: 4EA3; 5DHG; 5DHH; 8F7X
• Pfam ID: PF00001
• Sequence:
  MEPLFPAPFWEVIYGSHLQGNLSLLSPNHSLLPPHLLLNASHGAFLPLGLKVTIVGLYLA
  VCVGGLLGNCLVMYVILRHTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLGFWPFGN
  ALCKTVIAIDYYNMFTSTFTLTAMSVDRYVAICHPIRALDVRTSSKAQAVNVAIWALASV
  VGVPVAIMGSAQVEDEEIECLVEIPTPQDYWGPVFAICIFLFSFIVPVLVISVCYSLMIR
  RLRGVRLLSGSREKDRNLRRITRLVLVVVAVFVGCWTPVQVFVLAQGLGVQPSSETAVAI
  LRFCTALGYVNSCLNPILYAFLDENFKACFRKFCCASALRRDVQVSDRVRSIAKDVALAC
  KTSETVPRPA
• Function: G-protein coupled opioid receptor that functions as a receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.
• Tissue Specificity: Detected in blood leukocytes.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Nociceptin receptor (OPRL1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Nociceptin receptor (OPRL1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nociceptin receptor (OPRL1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nociceptin receptor (OPRL1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nociceptin receptor (OPRL1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Nociceptin receptor (OPRL1).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Nociceptin receptor (OPRL1).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Nociceptin receptor (OPRL1).	[6]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
NOCICEPTIN	DMUPA7C	Phase 1	NOCICEPTIN affects the binding of Nociceptin receptor (OPRL1).	[8]

References

• [1] 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.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] ?(9)-Tetrahydrocannabinol decreases NOP receptor density and mRNA levels in human SH-SY5Y cells. J Mol Neurosci. 2012 Feb;46(2):285-92. doi: 10.1007/s12031-011-9552-0. Epub 2011 May 21.
• [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.
• [8] Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine. J Med Chem. 2011 Oct 13;54(19):6531-7. doi: 10.1021/jm2003238. Epub 2011 Sep 7.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.