Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRWART5)

• DOT Name: Atrial natriuretic peptide receptor 1 (NPR1)
• Synonyms: EC 4.6.1.2; Atrial natriuretic peptide receptor type A; ANP-A; ANPR-A; NPR-A; Guanylate cyclase A; GC-A
• Gene Name: NPR1
• UniProt ID: ANPRA_HUMAN
• EC Number: 4.6.1.2
• Pfam ID: PF01094 ; PF00211 ; PF07714
• Sequence:
  MPGPRRPAGSRLRLLLLLLLPPLLLLLRGSHAGNLTVAVVLPLANTSYPWSWARVGPAVE
  LALAQVKARPDLLPGWTVRTVLGSSENALGVCSDTAAPLAAVDLKWEHNPAVFLGPGCVY
  AAAPVGRFTAHWRVPLLTAGAPALGFGVKDEYALTTRAGPSYAKLGDFVAALHRRLGWER
  QALMLYAYRPGDEEHCFFLVEGLFMRVRDRLNITVDHLEFAEDDLSHYTRLLRTMPRKGR
  VIYICSSPDAFRTLMLLALEAGLCGEDYVFFHLDIFGQSLQGGQGPAPRRPWERGDGQDV
  SARQAFQAAKIITYKDPDNPEYLEFLKQLKHLAYEQFNFTMEDGLVNTIPASFHDGLLLY
  IQAVTETLAHGGTVTDGENITQRMWNRSFQGVTGYLKIDSSGDRETDFSLWDMDPENGAF
  RVVLNYNGTSQELVAVSGRKLNWPLGYPPPDIPKCGFDNEDPACNQDHLSTLEVLALVGS
  LSLLGILIVSFFIYRKMQLEKELASELWRVRWEDVEPSSLERHLRSAGSRLTLSGRGSNY
  GSLLTTEGQFQVFAKTAYYKGNLVAVKRVNRKRIELTRKVLFELKHMRDVQNEHLTRFVG
  ACTDPPNICILTEYCPRGSLQDILENESITLDWMFRYSLTNDIVKGMLFLHNGAICSHGN
  LKSSNCVVDGRFVLKITDYGLESFRDLDPEQGHTVYAKKLWTAPELLRMASPPVRGSQAG
  DVYSFGIILQEIALRSGVFHVEGLDLSPKEIIERVTRGEQPPFRPSLALQSHLEELGLLM
  QRCWAEDPQERPPFQQIRLTLRKFNRENSSNILDNLLSRMEQYANNLEELVEERTQAYLE
  EKRKAEALLYQILPHSVAEQLKRGETVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTL
  LNDLYTCFDAVIDNFDVYKVETIGDAYMVVSGLPVRNGRLHACEVARMALALLDAVRSFR
  IRHRPQEQLRLRIGIHTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGEALKIHLSSET
  KAVLEEFGGFELELRGDVEMKGKGKVRTYWLLGERGSSTRG
• Function: Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Vascular smooth muscle contraction (hsa04270)
  Thermogenesis (hsa04714)
  Oxytocin sig.ling pathway (hsa04921)
  Regulation of lipolysis in adipocytes (hsa04923)
  Renin secretion (hsa04924)
  Aldosterone synthesis and secretion (hsa04925)
• Reactome Pathway: Physiological factors (R-HSA-5578768)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenytoin	DMNOKBV	Approved	Atrial natriuretic peptide receptor 1 (NPR1) increases the Cleft palate ADR of Phenytoin.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[7]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[10]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Atrial natriuretic peptide receptor 1 (NPR1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Atrial natriuretic peptide receptor 1 (NPR1).	[11]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [9] Genistein affects the expression of genes involved in blood pressure regulation and angiogenesis in primary human endothelial cells. Nutr Metab Cardiovasc Dis. 2006 Jan;16(1):35-43. doi: 10.1016/j.numecd.2005.03.003. Epub 2005 Jul 28.
• [10] 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.
• [11] 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.
• [12] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [13] 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.