Details of Drug Off-Target (DOT)

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

• DOT Name: Syntaxin-11 (STX11)
• Gene Name: STX11
• Related Disease:
  Familial hemophagocytic lymphohistiocytosis 4
  Acute myelogenous leukaemia
  Advanced cancer
  Inborn error of immunity
  Myelodysplastic syndrome
  Neoplasm
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Hereditary hemophagocytic lymphohistiocytosis
• UniProt ID: STX11_HUMAN
• Pfam ID: PF00804
• Sequence:
  MKDRLAELLDLSKQYDQQFPDGDDEFDSPHEDIVFETDHILESLYRDIRDIQDENQLLVA
  DVKRLGKQNARFLTSMRRLSSIKRDTNSIAKAIKARGEVIHCKLRAMKELSEAAEAQHGP
  HSAVARISRAQYNALTLTFQRAMHDYNQAEMKQRDNCKIRIQRQLEIMGKEVSGDQIEDM
  FEQGKWDVFSENLLADVKGARAALNEIESRHRELLRLESRIRDVHELFLQMAVLVEKQAD
  TLNVIELNVQKTVDYTGQAKAQVRKAVQYEEKNPCRTLCCFCCPCLK
• Function: SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial hemophagocytic lymphohistiocytosis 4	DISJ8FVK	Definitive	Autosomal recessive	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Inborn error of immunity	DISNGCMN	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[4]
Hereditary hemophagocytic lymphohistiocytosis	DISQP21Z	Supportive	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Syntaxin-11 (STX11).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Syntaxin-11 (STX11).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Syntaxin-11 (STX11).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Syntaxin-11 (STX11).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Syntaxin-11 (STX11).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Syntaxin-11 (STX11).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Syntaxin-11 (STX11).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Syntaxin-11 (STX11).	[12]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Syntaxin-11 (STX11).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Syntaxin-11 (STX11).	[14]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Syntaxin-11 (STX11).	[15]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Syntaxin-11 (STX11).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Syntaxin-11 (STX11).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntaxin-11 (STX11).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Syntaxin-11 (STX11).	[20]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Spectrum and clinical implications of syntaxin 11 gene mutations in familial haemophagocytic lymphohistiocytosis: association with disease-free remissions and haematopoietic malignancies.J Med Genet. 2006 Apr;43(4):e14. doi: 10.1136/jmg.2005.035253.
• [3] Munc18-2 is required for Syntaxin 11 Localization on the Plasma Membrane in Cytotoxic T-Lymphocytes.Traffic. 2015 Dec;16(12):1330-41. doi: 10.1111/tra.12337. Epub 2015 Nov 2.
• [4] STX11 functions as a novel tumor suppressor gene in peripheral T-cell lymphomas.Cancer Sci. 2015 Oct;106(10):1455-62. doi: 10.1111/cas.12742. Epub 2015 Aug 13.
• [5] Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. Am J Hum Genet. 2001 Mar;68(3):590-7. doi: 10.1086/318796. Epub 2001 Feb 6.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] 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.
• [12] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [13] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [16] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [19] 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.
• [20] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.