Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUEY1FM)

• DOT Name: Homeobox protein NANOG (NANOG)
• Synonyms: Homeobox transcription factor Nanog; hNanog
• Gene Name: NANOG
• Related Disease:
  Acute myelogenous leukaemia
  Cervical cancer
  Adenocarcinoma
  Adult teratoma
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Breast neoplasm
  Carcinoma
  Colon carcinoma
  Embryonal neoplasm
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Germ cell tumor
  Hepatocellular carcinoma
  Herpes simplex infection
  leukaemia
  Leukemia
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate neoplasm
  Schizophrenia
  Seminoma
  Teratoma
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Clear cell renal carcinoma
  Colon cancer
  Glioblastoma multiforme
  Lung adenocarcinoma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Adult glioblastoma
  Carcinoma of liver and intrahepatic biliary tract
  Cervical carcinoma
  Hepatitis C virus infection
  Liver cancer
  Lung cancer
  Neuroblastoma
  Non-small-cell lung cancer
  Squamous cell carcinoma
• UniProt ID: NANOG_HUMAN
• PDB ID: 2KT0; 4RBO
• Pfam ID: PF00046
• Sequence:
  MSVDPACPQSLPCFEASDCKESSPMPVICGPEENYPSLQMSSAEMPHTETVSPLPSSMDL
  LIQDSPDSSTSPKGKQPTSAEKSVAKKEDKVPVKKQKTRTVFSSTQLCVLNDRFQRQKYL
  SLQQMQELSNILNLSYKQVKTWFQNQRMKSKRWQKNNWPKNSNGVTQKASAPTYPSLYSS
  YHQGCLVNPTGNLPMWSNQTWNNSTWSNQTQNIQSWSNHSWNTQTWCTQSWNNQAWNSPF
  YNCGEESLQSCMQFQPNSPASDLEAALEAAGEGLNVIQQTTRYFSTPQTMDLFLNYSMNM
  QPEDV
• Function: Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal. Imposes pluripotency on ES cells and prevents their differentiation towards extraembryonic endoderm and trophectoderm lineages. Blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes. Acts as a transcriptional activator or repressor. Binds optimally to the DNA consensus sequence 5'-TAAT[GT][GT]-3' or 5'-[CG][GA][CG]C[GC]ATTAN[GC]-3'. Binds to the POU5F1/OCT4 promoter. Able to autorepress its expression in differentiating (ES) cells: binds to its own promoter following interaction with ZNF281/ZFP281, leading to recruitment of the NuRD complex and subsequent repression of expression. When overexpressed, promotes cells to enter into S phase and proliferation.
• Tissue Specificity: Expressed in testicular carcinoma and derived germ cell tumors (at protein level). Expressed in fetal gonads, ovary and testis. Also expressed in ovary teratocarcinoma cell line and testicular embryonic carcinoma. Not expressed in many somatic organs and oocytes.
• KEGG Pathway:
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (R-HSA-2892247)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Germ layer formation at gastrulation (R-HSA-9754189)
  Formation of the anterior neural plate (R-HSA-9823739)
  Specification of primordial germ cells (R-HSA-9827857)
  POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation (R-HSA-2892245)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Cervical cancer	DISFSHPF	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adult teratoma	DISBY81U	Strong	Posttranslational Modification	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Carcinoma	DISH9F1N	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Embryonal neoplasm	DIS5MQSB	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Germ cell tumor	DIS62070	Strong	Posttranslational Modification	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
Herpes simplex infection	DISL1SAV	Strong	Genetic Variation	[15]
leukaemia	DISS7D1V	Strong	Genetic Variation	[16]
Leukemia	DISNAKFL	Strong	Genetic Variation	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[20]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[21]
Seminoma	DIS3J8LJ	Strong	Genetic Variation	[4]
Teratoma	DIS6ICY4	Strong	Biomarker	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[7]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[24]
Colon cancer	DISVC52G	moderate	Biomarker	[5]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[25]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[26]
Pancreatic cancer	DISJC981	moderate	Biomarker	[27]
Prostate cancer	DISF190Y	moderate	Altered Expression	[28]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[28]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[24]
Adult glioblastoma	DISVP4LU	Disputed	Biomarker	[25]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[29]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[30]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[31]
Liver cancer	DISDE4BI	Limited	Biomarker	[29]
Lung cancer	DISCM4YA	Limited	Biomarker	[17]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[32]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[33]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[34]

41 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 Homeobox protein NANOG (NANOG).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein NANOG (NANOG).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Homeobox protein NANOG (NANOG).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Homeobox protein NANOG (NANOG).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Homeobox protein NANOG (NANOG).	[39]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Homeobox protein NANOG (NANOG).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Homeobox protein NANOG (NANOG).	[41]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Homeobox protein NANOG (NANOG).	[42]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Homeobox protein NANOG (NANOG).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Homeobox protein NANOG (NANOG).	[37]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Homeobox protein NANOG (NANOG).	[43]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Homeobox protein NANOG (NANOG).	[44]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Homeobox protein NANOG (NANOG).	[45]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Homeobox protein NANOG (NANOG).	[46]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Homeobox protein NANOG (NANOG).	[47]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Homeobox protein NANOG (NANOG).	[43]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Homeobox protein NANOG (NANOG).	[48]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR increases the expression of Homeobox protein NANOG (NANOG).	[49]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Homeobox protein NANOG (NANOG).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein NANOG (NANOG).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Homeobox protein NANOG (NANOG).	[51]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of Homeobox protein NANOG (NANOG).	[52]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Homeobox protein NANOG (NANOG).	[48]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of Homeobox protein NANOG (NANOG).	[53]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Homeobox protein NANOG (NANOG).	[44]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Homeobox protein NANOG (NANOG).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein NANOG (NANOG).	[55]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Homeobox protein NANOG (NANOG).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Homeobox protein NANOG (NANOG).	[57]
CHIR-99021	DMB8MNU	Patented	CHIR-99021 decreases the expression of Homeobox protein NANOG (NANOG).	[58]
ABT-737	DML0DBV	Terminated	ABT-737 decreases the expression of Homeobox protein NANOG (NANOG).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Homeobox protein NANOG (NANOG).	[60]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Homeobox protein NANOG (NANOG).	[61]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Homeobox protein NANOG (NANOG).	[45]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Homeobox protein NANOG (NANOG).	[62]
Cordycepin	DM72Y01	Investigative	Cordycepin affects the expression of Homeobox protein NANOG (NANOG).	[63]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Homeobox protein NANOG (NANOG).	[64]
Kaempferol	DMHEMUB	Investigative	Kaempferol decreases the expression of Homeobox protein NANOG (NANOG).	[65]
Apigenin	DMI3491	Investigative	Apigenin decreases the expression of Homeobox protein NANOG (NANOG).	[66]
Ginsenoside RG3	DMFN58T	Investigative	Ginsenoside RG3 decreases the expression of Homeobox protein NANOG (NANOG).	[67]
CHIR-98014	DMVEBT6	Investigative	CHIR-98014 decreases the expression of Homeobox protein NANOG (NANOG).	[61]

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 Homeobox protein NANOG (NANOG).	[54]

References

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