Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZS4SKF)

• DOT Name: Sushi domain-containing protein 6 (SUSD6)
• Synonyms: Drug-activated gene overexpressed protein
• Gene Name: SUSD6
• Related Disease:
  Non-small-cell lung cancer
  Colorectal carcinoma
  Neoplasm
• UniProt ID: SUSD6_HUMAN
• Pfam ID: PF00084
• Sequence:
  MCHGRIAPKSTSVFAVASVGHGVFLPLVILCTLLGDGLASVCPLPPEPENGGYICHPRPC
  RDPLTAGSVIEYLCAEGYMLKGDYKYLTCKNGEWKPAMEISCRLNEDKDTHTSLGVPTLS
  IVASTASSVALILLLVVLFVLLQPKLKSFHHSRRDQGVSGDQVSIMVDGVQVALPSYEEA
  VYGSSGHCVPPADPRVQIVLSEGSGPSGRSVPREQQLPDQGACSSAGGEDEAPGQSGLCE
  AWGSRASETVMVHQATTSSWVAGSGNRQLAHKETADSENSDIQSLLSLTSEEYTDDIPLL
  KEA
• Function: May play a role in growth-suppressive activity and cell death. May be involved in the production of chemokine molecules in umbilical vein endothelial cells (HUVECs) cultured in THP1 monocyte LPS-induced medium. Plays a role in preventing tumor onset.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitazoxanide	DMOWLVG	Approved	Sushi domain-containing protein 6 (SUSD6) affects the response to substance of Nitazoxanide.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sushi domain-containing protein 6 (SUSD6).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sushi domain-containing protein 6 (SUSD6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sushi domain-containing protein 6 (SUSD6).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sushi domain-containing protein 6 (SUSD6).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sushi domain-containing protein 6 (SUSD6).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sushi domain-containing protein 6 (SUSD6).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sushi domain-containing protein 6 (SUSD6).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Sushi domain-containing protein 6 (SUSD6).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sushi domain-containing protein 6 (SUSD6).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sushi domain-containing protein 6 (SUSD6).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Sushi domain-containing protein 6 (SUSD6).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Sushi domain-containing protein 6 (SUSD6).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Sushi domain-containing protein 6 (SUSD6).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sushi domain-containing protein 6 (SUSD6).	[10]
biochanin A	DM0HPWY	Investigative	biochanin A increases the expression of Sushi domain-containing protein 6 (SUSD6).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sushi domain-containing protein 6 (SUSD6).	[13]

References

• [1] KIAA0247 inhibits growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway.Cancer Sci. 2018 Apr;109(4):1055-1065. doi: 10.1111/cas.13539. Epub 2018 Mar 25.
• [2] A predicted protein, KIAA0247, is a cell cycle modulator in colorectal cancer cells under 5-FU treatment.J Transl Med. 2011 May 28;9:82. doi: 10.1186/1479-5876-9-82.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.
• [17] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.