Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT164PA1)

• DOT Name: Delta-type opioid receptor (OPRD1)
• Synonyms: D-OR-1; DOR-1
• Gene Name: OPRD1
• UniProt ID: OPRD_HUMAN
• PDB ID: 4N6H; 4RWA; 4RWD; 6PT2; 6PT3; 8F7S
• Pfam ID: PF00001
• Sequence:
  MEPAPSAGAELQPPLFANASDAYPSACPSAGANASGPPGARSASSLALAIAITALYSAVC
  AVGLLGNVLVMFGIVRYTKMKTATNIYIFNLALADALATSTLPFQSAKYLMETWPFGELL
  CKAVLSIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPAKAKLINICIWVLASGVG
  VPIMVMAVTRPRDGAVVCMLQFPSPSWYWDTVTKICVFLFAFVVPILIITVCYGLMLLRL
  RSVRLLSGSKEKDRSLRRITRMVLVVVGAFVVCWAPIHIFVIVWTLVDIDRRDPLVVAAL
  HLCIALGYANSSLNPVLYAFLDENFKRCFRQLCRKPCGRPDPSSFSRAREATARERVTAC
  TPSDGPGGGAAA
• Function: G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
• Tissue Specificity: Detected in oocytes (at protein level). Detected in brain cortex, hypothalamus, hippocampus and olfactory bulb. Detected in oocytes.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  Sphingolipid sig.ling pathway (hsa04071)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Clonidine	DM6RZ9Q	Approved	Delta-type opioid receptor (OPRD1) increases the Adverse drug reaction ADR of Clonidine.	[7]
Pilocarpine	DMV9ADG	Approved	Delta-type opioid receptor (OPRD1) increases the Seizures (incl subtypes) ADR of Pilocarpine.	[7]

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 Delta-type opioid receptor (OPRD1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Delta-type opioid receptor (OPRD1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Delta-type opioid receptor (OPRD1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Delta-type opioid receptor (OPRD1).	[2]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Delta-type opioid receptor (OPRD1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DPDPE	DMIRSNA	Investigative	DPDPE affects the binding of Delta-type opioid receptor (OPRD1).	[6]

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] 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.
• [3] 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.
• [4] 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.
• [5] Proteasome subunit and opioid receptor gene expression down-regulation induced by paraquat and maneb in human neuroblastoma SH-SY5Y cells. Environ Toxicol Pharmacol. 2015 Nov;40(3):895-900. doi: 10.1016/j.etap.2015.09.019. Epub 2015 Oct 3.
• [6] 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.
• [7] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.