Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXS0EXM)

• DOT Name: Suppressor APC domain-containing protein 2 (SAPCD2)
• Synonyms: Tumor specificity and mitosis phase-dependent expression protein; TS/MDEP; p42.3
• Gene Name: SAPCD2
• Related Disease:
  Colorectal carcinoma
  Nasopharyngeal carcinoma
• UniProt ID: SAPC2_HUMAN
• Pfam ID: PF11414
• Sequence:
  MAGAAMAERGRVPPPAPAPSTEGLPRAFLQSLRTLFDILDDRRRGCVHLREIESRWQGTD
  ARELPRGVLEGLRQVAPASGYLTFERFVAGLRTSLLSADGGPRDPTRAPARPGDQPPPPP
  QRLVFAPADEPRTVLERKPLPLGVRAPLAGPSAAARSPEQLCAPAEAAPCPAEPERSQSA
  ALEPSSSADAGAVACRALEADSGDARRAPRARGERRRHTIASGVDCGLLKQMKELEQEKE
  VLLQGLEMMARGRDWYQQQLQRVQERQRRLGQSRASADFGAAGSPRPLGRLLPKVQEVAR
  CLGELLAAACASRALPPSSSGPPCPALTSTSPPVWQQQTILMLKEQNRLLTQEVTEKSER
  ITQLEQEKSALIKQLFEARALSQQDGGPLDSTFI
• Function: Plays a role in planar mitotic spindle orientation in retinal progenitor cells (RPCs) and promotes the production of symmetric terminal divisions. Negatively regulates the mitotic apical cortex localization of GPSM2. Involved also in positive regulation of cell proliferation and tumor cell growth.
• Tissue Specificity: Expressed in 5-month-old fetal tissues, including stomach, intestine, colon, liver, brain, lung, heart, spleen and kidney . Undetectable in non-cancerous adult tissues . Expressed in many primary gastric carcinoma, but almost not in adjacent normal mucosa . Expressed preferentially in M and G1 phases, compared to S and G2 phases . Expression is up-regulated in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) tissues (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[14]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[17]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Suppressor APC domain-containing protein 2 (SAPCD2).	[19]

References

• [1] Role of C9orf140 in the promotion of colorectal cancer progression and mechanisms of its upregulation via activation of STAT5, -catenin and EZH2.Carcinogenesis. 2014 Jun;35(6):1389-98. doi: 10.1093/carcin/bgu057. Epub 2014 Mar 6.
• [2] Long noncoding RNA PXN-AS1-L promotes the malignancy of nasopharyngeal carcinoma cells via upregulation of SAPCD2.Cancer Med. 2019 Aug;8(9):4278-4291. doi: 10.1002/cam4.2227. Epub 2019 Jun 7.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [10] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [15] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.