Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEQU0V7)

• DOT Name: Uncharacterized protein C11orf96 (C11ORF96)
• Synonyms: Protein Ag2 homolog
• Gene Name: C11ORF96
• Related Disease:
  Carotid stenosis
  Hepatocellular carcinoma
• UniProt ID: CK096_HUMAN
• Pfam ID: PF15766
• Sequence:
  MGNKQPQKVTVPTGTALQGVVLIVSTLHQPGGWICGKDPCCSLRPLSNSVQNALACKSKQ
  DYQAGILFKTRAFISRDCGSDAAEDSASKGETYTLTLEHKGAGEGDLRPRGQPGWCRLGD
  PRRDSARPVAAIEGPCPGAARASRVLRGRGFSRNPRGRGLPSGAGWRGAGGAGEGAVTFP
  ERRGDVRRKGAGRARFKWHSLSSELRAVWAAAGYISREPGRRGADGDSSGGERLGARRNS
  APRAPCPPTGPPARPPSRGAPARAREGRRHPAADLDPPPGEPPAAASRGAPAQRPPSESP
  GAPPPGPADAGGAMAAKPGELMGICSSYQAVMPHFVCLADEFPQPVRPAKLPKGRGRLRR
  PRQSRFKTQPVTFDEIQEVEEEGVSPMEEEKAKKSFLQSLECLRRSTQSLSLQREQLSSC
  KLRNSLDSSDSDSAL

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carotid stenosis	DISZA8D0	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[2]

23 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 Uncharacterized protein C11orf96 (C11ORF96).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Uncharacterized protein C11orf96 (C11ORF96).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Uncharacterized protein C11orf96 (C11ORF96).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[14]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[18]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[22]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Uncharacterized protein C11orf96 (C11ORF96).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Uncharacterized protein C11orf96 (C11ORF96).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Uncharacterized protein C11orf96 (C11ORF96).	[17]

References

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• [2] Novel angiotensin receptor blocker, azilsartan induces oxidative stress and NFkB-mediated apoptosis in hepatocellular carcinoma cell line HepG2.Biomed Pharmacother. 2018 Mar;99:939-946. doi: 10.1016/j.biopha.2018.01.117. Epub 2018 Feb 20.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] 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.
• [12] 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.
• [13] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [14] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [15] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.
• [19] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [20] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [21] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [22] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [23] Roles of acyl-CoA synthetase long-chain family member 5 and colony stimulating factor 2 in inhibition of palmitic or stearic acids in lung cancer cell proliferation and metabolism. Cell Biol Toxicol. 2021 Feb;37(1):15-34. doi: 10.1007/s10565-020-09520-w. Epub 2020 Apr 28.