Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSDFA2D)

• DOT Name: Sperm-associated antigen 7 (SPAG7)
• Gene Name: SPAG7
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Periodic fever syndrome
• UniProt ID: SPAG7_HUMAN
• PDB ID: 2CPM
• Pfam ID: PF01424
• Sequence:
  MADLLGSILSSMEKPPSLGDQETRRKAREQAARLKKLQEQEKQQKVEFRKRMEKEVSDFI
  QDSGQIKKKFQPMNKIERSILHDVVEVAGLTSFSFGEDDDCRYVMIFKKEFAPSDEELDS
  YRRGEEWDPQKAEEKRKLKELAQRQEEEAAQQGPVVVSPASDYKDKYSHLIGKGAAKDAA
  HMLQANKTYGCVPVANKRDTRSIEEAMNEIRAKKRLRQSGEELPPTS
• Tissue Specificity: Detected in fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Periodic fever syndrome	DIS9MNYC	Limited	Genetic Variation	[2]

10 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 Sperm-associated antigen 7 (SPAG7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Sperm-associated antigen 7 (SPAG7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sperm-associated antigen 7 (SPAG7).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Sperm-associated antigen 7 (SPAG7).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Sperm-associated antigen 7 (SPAG7).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sperm-associated antigen 7 (SPAG7).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Sperm-associated antigen 7 (SPAG7).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sperm-associated antigen 7 (SPAG7).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sperm-associated antigen 7 (SPAG7).	[11]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Sperm-associated antigen 7 (SPAG7).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sperm-associated antigen 7 (SPAG7).	[10]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Sperm-associated antigen 7 (SPAG7).	[13]

References

• [1] Amazon Fruits Inhibit Growth and Promote Pro-apoptotic Effects on Human Ovarian Carcinoma Cell Lines.Biomolecules. 2019 Nov 6;9(11):707. doi: 10.3390/biom9110707.
• [2] SPAG7 is a candidate gene for the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome.Genes Immun. 2014 Apr-May;15(3):190-4. doi: 10.1038/gene.2013.73. Epub 2014 Jan 23.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
• [13] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.