Details of Drug Off-Target (DOT)

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

• DOT Name: D(1B) dopamine receptor (DRD5)
• Synonyms: D(5) dopamine receptor; D1beta dopamine receptor; Dopamine D5 receptor
• Gene Name: DRD5
• Related Disease: Attention deficit hyperactivity disorder
• UniProt ID: DRD5_HUMAN
• PDB ID: 8IRV
• Pfam ID: PF00001
• Sequence:
  MLPPGSNGTAYPGQFALYQQLAQGNAVGGSAGAPPLGPSQVVTACLLTLLIIWTLLGNVL
  VCAAIVRSRHLRANMTNVFIVSLAVSDLFVALLVMPWKAVAEVAGYWPFGAFCDVWVAFD
  IMCSTASILNLCVISVDRYWAISRPFRYKRKMTQRMALVMVGLAWTLSILISFIPVQLNW
  HRDQAASWGGLDLPNNLANWTPWEEDFWEPDVNAENCDSSLNRTYAISSSLISFYIPVAI
  MIVTYTRIYRIAQVQIRRISSLERAAEHAQSCRSSAACAPDTSLRASIKKETKVLKTLSV
  IMGVFVCCWLPFFILNCMVPFCSGHPEGPPAGFPCVSETTFDVFVWFGWANSSLNPVIYA
  FNADFQKVFAQLLGCSHFCSRTPVETVNISNELISYNQDIVFHKEIAAAYIHMMPNAVTP
  GNREVDNDEEEGPFDRMFQIYQTSPDGDPVAESVWELDCEGEISLDKITPFTPNGFH
• Function: Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
• Tissue Specificity: Neuron-specific, localized primarily within limbic regions of the brain.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Dopaminergic sy.pse (hsa04728)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Dopamine receptors (R-HSA-390651)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	No Known	Unknown	[1]

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 D(1B) dopamine receptor (DRD5).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of D(1B) dopamine receptor (DRD5).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of D(1B) dopamine receptor (DRD5).	[3]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of D(1B) dopamine receptor (DRD5).	[5]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of D(1B) dopamine receptor (DRD5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
LE-300	DMGJL16	Preclinical	LE-300 affects the binding of D(1B) dopamine receptor (DRD5).	[7]

References

• [1] Meta-analysis of the DRD5 VNTR in persistent ADHD. Eur Neuropsychopharmacol. 2016 Sep;26(9):1527-1532. doi: 10.1016/j.euroneuro.2016.06.012. Epub 2016 Jul 29.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] Chiral indolo[3,2-f][3]benzazecine-type dopamine receptor antagonists: synthesis and activity of racemic and enantiopure derivatives. J Med Chem. 2011 Oct 27;54(20):7422-6. doi: 10.1021/jm200676f. Epub 2011 Sep 29.