Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT76JZ8Z)

• DOT Name: Serum amyloid P-component (APCS)
• Synonyms: SAP; 9.5S alpha-1-glycoprotein
• Gene Name: APCS
• UniProt ID: SAMP_HUMAN
• PDB ID: 1GYK; 1LGN; 1SAC; 2A3W; 2A3X; 2A3Y; 2W08; 3D5O; 3KQR; 4AVS; 4AVT; 4AVV; 4AYU
• Pfam ID: PF00354
• Sequence:
  MNKPLLWISVLTSLLEAFAHTDLSGKVFVFPRESVTDHVNLITPLEKPLQNFTLCFRAYS
  DLSRAYSLFSYNTQGRDNELLVYKERVGEYSLYIGRHKVTSKVIEKFPAPVHICVSWESS
  SGIAEFWINGTPLVKKGLRQGYFVEAQPKIVLGQEQDSYGGKFDRSQSFVGEIGDLYMWD
  SVLPPENILSAYQGTPLPANILDWQALNYEIRGYVIIKPLVWV
• Function: Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin.
• Tissue Specificity: Found in serum and urine.
• Reactome Pathway: Amyloid fiber formation (R-HSA-977225)

Molecular Interaction Atlas (MIA) of This DOT

8 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 Serum amyloid P-component (APCS).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serum amyloid P-component (APCS).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Serum amyloid P-component (APCS).	[1]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Serum amyloid P-component (APCS).	[4]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Serum amyloid P-component (APCS).	[5]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Serum amyloid P-component (APCS).	[6]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the expression of Serum amyloid P-component (APCS).	[7]
Valsartan	DMREUQ6	Approved	Valsartan decreases the expression of Serum amyloid P-component (APCS).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serum amyloid P-component (APCS).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serum amyloid P-component (APCS).	[9]

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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [5] Elevated C-reactive protein levels are associated with endothelial dysfunction in chronic cocaine users. Int J Cardiol. 2003 Apr;88(2-3):191-8. doi: 10.1016/s0167-5273(02)00394-7.
• [6] Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
• [7] Acute effect of standard heparin versus low molecular weight heparin on oxidative stress and inflammation in hemodialysis patients. Ren Fail. 2006;28(8):723-7. doi: 10.1080/08860220600925594.
• [8] C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation. 2005 Sep 6;112(10):1428-34. doi: 10.1161/CIRCULATIONAHA.104.508465. Epub 2005 Aug 29.
• [9] 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.