Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7NRCY)

• DOT Name: Protein SSX1 (SSX1)
• Synonyms: Cancer/testis antigen 5.1; CT5.1; Synovial sarcoma, X breakpoint 1
• Gene Name: SSX1
• Related Disease:
  Ewing sarcoma
  Classic Hodgkin lymphoma
  Desmoplastic small round cell tumor
  Hepatocellular carcinoma
  Malignant soft tissue neoplasm
  Metastatic malignant neoplasm
  Plasma cell myeloma
  Soft tissue neoplasm
  Spermatogenic failure, X-linked, 5
  Melanoma
  Rhabdomyosarcoma
  Soft tissue sarcoma
  Testicular cancer
  Sarcoma
• UniProt ID: SSX1_HUMAN
• Pfam ID: PF09514
• Sequence:
  MNGDDTFAKRPRDDAKASEKRSKAFDDIATYFSKKEWKKMKYSEKISYVYMKRNYKAMTK
  LGFKVTLPPFMCNKQATDFQGNDFDNDHNRRIQVEHPQMTFGRLHRIIPKIMPKKPAEDE
  NDSKGVSEASGPQNDGKQLHPPGKANISEKINKRSGPKRGKHAWTHRLRERKQLVIYEEI
  SDPEEDDE
• Function: Could act as a modulator of transcription. Plays a role in spermatogenesis.
• Tissue Specificity: Expressed at high level in the testis. Expressed at low level in thyroid. Not detected in tonsil, colon, lung, spleen, prostate, kidney, striated and smooth muscles. Detected in rhabdomyosarcoma and fibrosarcoma cell lines. Not detected in mesenchymal and epithelial cell lines . Expressed in testis .
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ewing sarcoma	DISQYLV3	Definitive	Biomarker	[1]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[2]
Desmoplastic small round cell tumor	DISLI2ME	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Genetic Variation	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[6]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[7]
Soft tissue neoplasm	DISP2OHE	Strong	Genetic Variation	[3]
Spermatogenic failure, X-linked, 5	DISS7QW6	Strong	X-linked	[8]
Melanoma	DIS1RRCY	moderate	Biomarker	[9]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[10]
Soft tissue sarcoma	DISSN8XB	moderate	Genetic Variation	[11]
Testicular cancer	DIS6HNYO	moderate	Altered Expression	[12]
Sarcoma	DISZDG3U	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein SSX1 (SSX1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein SSX1 (SSX1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein SSX1 (SSX1).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein SSX1 (SSX1).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein SSX1 (SSX1).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Protein SSX1 (SSX1).	[19]

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 decreases the methylation of Protein SSX1 (SSX1).	[17]

References

• [1] NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis.Mod Pathol. 2012 Jun;25(6):854-8. doi: 10.1038/modpathol.2012.31. Epub 2012 Mar 2.
• [2] Expression of SSX genes in the neoplastic cells of Hodgkin's lymphoma.Hum Pathol. 2002 May;33(5):496-502. doi: 10.1053/hupa.2002.124909.
• [3] Immunohistochemical and molecular genetic approaches to soft tissue tumor diagnosis: a primer.Semin Oncol. 1997 Oct;24(5):515-25.
• [4] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [5] Detection of SYT-SSX rearrangements in synovial sarcomas by real-time one-step RT-PCR.Pediatr Dev Pathol. 2005 Mar-Apr;8(2):162-7. doi: 10.1007/s10024-004-8097-4. Epub 2005 Mar 8.
• [6] Clinical impact of molecular and cytogenetic findings in synovial sarcoma.Genes Chromosomes Cancer. 2001 Aug;31(4):362-72. doi: 10.1002/gcc.1155.
• [7] SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs.J Immunother. 2005 Nov-Dec;28(6):564-75. doi: 10.1097/01.cji.0000175685.36239.e5.
• [8] Deficiency of primate-specific SSX1 induced asthenoteratozoospermia in infertile men and cynomolgus monkey and tree shrew models. Am J Hum Genet. 2023 Mar 2;110(3):516-530. doi: 10.1016/j.ajhg.2023.01.016. Epub 2023 Feb 15.
• [9] Identification of unique sensitizing targets for anti-inflammatory CDDO-Me in metastatic melanoma by a large-scale synthetic lethal RNAi screening.Pigment Cell Melanoma Res. 2013 Jan;26(1):97-112. doi: 10.1111/pcmr.12031. Epub 2012 Nov 6.
• [10] Differentiating Ewing's sarcoma from other round blue cell tumors using a RT-PCR translocation panel on formalin-fixed paraffin-embedded tissues.Mod Pathol. 2007 Mar;20(3):397-404. doi: 10.1038/modpathol.3800755.
• [11] Real-time polymerase chain reaction as an aid for the detection of SYT-SSX1 and SYT-SSX2 transcripts in fresh and archival pediatric synovial sarcoma specimens: report of 25 cases from St. Jude Children's Research Hospital.Pediatr Dev Pathol. 2003 Jan-Feb;6(1):24-34. doi: 10.1007/s10024-002-0050-9. Epub 2002 Dec 10.
• [12] Comparisons for detecting NY-ESO-1 mRNA expression levels in hepatocellular carcinoma tissues.Oncol Rep. 2009 Mar;21(3):713-9.
• [13] 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.
• [14] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [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] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [19] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.