Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT0W0LE)

• DOT Name: Transcription factor SOX-6 (SOX6)
• Gene Name: SOX6
• Related Disease:
  Esophageal squamous cell carcinoma
  Microphthalmia
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  B-cell neoplasm
  Beta thalassemia
  Carcinoma of esophagus
  Cardiovascular disease
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal cancer
  Glioma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Melanoma
  Mood disorder
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obesity
  Osteoporosis
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Tolchin-Le Caignec syndrome
  Type-1/2 diabetes
  Chronic obstructive pulmonary disease
  Coronary heart disease
  Osteoarthritis
  Pancreatic cancer
  Plasma cell myeloma
  Bone osteosarcoma
  Neuroblastoma
  Osteosarcoma
  Arteriosclerosis
  Atherosclerosis
  Hepatocellular carcinoma
  Non-insulin dependent diabetes
• UniProt ID: SOX6_HUMAN
• Pfam ID: PF00505
• Sequence:
  MSSKQATSPFACAADGEDAMTQDLTSREKEEGSDQHVASHLPLHPIMHNKPHSEELPTLV
  STIQQDADWDSVLSSQQRMESENNKLCSLYSFRNTSTSPHKPDEGSRDREIMTSVTFGTP
  ERRKGSLADVVDTLKQKKLEEMTRTEQEDSSCMEKLLSKDWKEKMERLNTSELLGEIKGT
  PESLAEKERQLSTMITQLISLREQLLAAHDEQKKLAASQIEKQRQQMDLARQQQEQIARQ
  QQQLLQQQHKINLLQQQIQVQGHMPPLMIPIFPHDQRTLAAAAAAQQGFLFPPGITYKPG
  DNYPVQFIPSTMAAAAASGLSPLQLQKGHVSHPQINQRLKGLSDRFGRNLDTFEHGGGHS
  YNHKQIEQLYAAQLASMQVSPGAKMPSTPQPPNTAGTVSPTGIKNEKRGTSPVTQVKDEA
  AAQPLNLSSRPKTAEPVKSPTSPTQNLFPASKTSPVNLPNKSSIPSPIGGSLGRGSSLDI
  LSSLNSPALFGDQDTVMKAIQEARKMREQIQREQQQQQPHGVDGKLSSINNMGLNSCRNE
  KERTRFENLGPQLTGKSNEDGKLGPGVIDLTRPEDAEGSKAMNGSAAKLQQYYCWPTGGA
  TVAEARVYRDARGRASSEPHIKRPMNAFMVWAKDERRKILQAFPDMHNSNISKILGSRWK
  SMSNQEKQPYYEEQARLSKIHLEKYPNYKYKPRPKRTCIVDGKKLRIGEYKQLMRSRRQE
  MRQFFTVGQQPQIPITTGTGVVYPGAITMATTTPSPQMTSDCSSTSASPEPSLPVIQSTY
  GMKTDGGSLAGNEMINGEDEMEMYDDYEDDPKSDYSSENEAPEAVSAN
• Function: Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation (Probable). Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX5, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube. Binds to the gene promoter of MBP and acts as a transcriptional repressor.
• Tissue Specificity: Expressed in a wide variety of tissues, most abundantly in skeletal musclen.
• Reactome Pathway: Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Altered Expression	[1]
Microphthalmia	DISGEBES	Definitive	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
B-cell neoplasm	DISVY326	Strong	Biomarker	[6]
Beta thalassemia	DIS5RCQK	Strong	Altered Expression	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[10]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
leukaemia	DISS7D1V	Strong	Biomarker	[3]
Leukemia	DISNAKFL	Strong	Genetic Variation	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Melanoma	DIS1RRCY	Strong	Biomarker	[13]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[15]
Obesity	DIS47Y1K	Strong	Biomarker	[16]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[16]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[17]
Tolchin-Le Caignec syndrome	DIS56G2R	Strong	Autosomal dominant	[18]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[19]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[20]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[21]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[22]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[23]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[24]
Bone osteosarcoma	DIST1004	Disputed	Biomarker	[25]
Neuroblastoma	DISVZBI4	Disputed	Biomarker	[26]
Osteosarcoma	DISLQ7E2	Disputed	Biomarker	[25]
Arteriosclerosis	DISK5QGC	Limited	Genetic Variation	[27]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[27]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[28]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[27]

11 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 Transcription factor SOX-6 (SOX6).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor SOX-6 (SOX6).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor SOX-6 (SOX6).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor SOX-6 (SOX6).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor SOX-6 (SOX6).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription factor SOX-6 (SOX6).	[34]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transcription factor SOX-6 (SOX6).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor SOX-6 (SOX6).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor SOX-6 (SOX6).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor SOX-6 (SOX6).	[39]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Transcription factor SOX-6 (SOX6).	[41]

3 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 Transcription factor SOX-6 (SOX6).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transcription factor SOX-6 (SOX6).	[37]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transcription factor SOX-6 (SOX6).	[40]

References

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• [17] miR-671 promotes prostate cancer cell proliferation by targeting tumor suppressor SOX6.Eur J Pharmacol. 2018 Mar 15;823:65-71. doi: 10.1016/j.ejphar.2018.01.016. Epub 2018 Jan 31.
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• [34] 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.
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• [41] Circ_0123996 promotes the proliferation, inflammation, and fibrosis of mesangial cells by sponging miR-203a-3p to upregulate SOX6 in diabetic nephropathy. J Biochem Mol Toxicol. 2022 Nov;36(11):e23139. doi: 10.1002/jbt.23139. Epub 2022 Sep 8.