Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU1LCNJ)

• DOT Name: Homeobox protein cut-like 1 (CUX1)
• Synonyms: CCAAT displacement protein; CDP; CDP/Cux p200; Homeobox protein cux-1
• Gene Name: CUX1
• Related Disease:
  B-cell lymphoma
  Matthew-Wood syndrome
  Multiple sclerosis
  Pancreatic cancer
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Depression
  Global developmental delay with or without impaired intellectual development
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Huntington disease
  Leiomyoma
  Leukemia
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Melanoma
  Myelodysplastic syndrome
  Parkinson disease
  Plasma cell myeloma
  Polycystic kidney disease
  Retinoblastoma
  Schizophrenia
  Squamous cell carcinoma
  Type-1/2 diabetes
  Uterine fibroids
  Glioma
  Autosomal dominant non-syndromic intellectual disability
  Colitis
  Cognitive impairment
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
  Myeloid leukaemia
  Nervous system disease
  Neuroblastoma
  Non-small-cell lung cancer
  Optic neuritis
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  T-cell leukaemia
• UniProt ID: CUX1_HUMAN
• Pfam ID: PF02376 ; PF00046
• Sequence:
  MLCVAGARLKRELDATATVLANRQDESEQSRKRLIEQSREFKKNTPEDLRKQVAPLLKSF
  QGEIDALSKRSKEAEAAFLNVYKRLIDVPDPVPALDLGQQLQLKVQRLHDIETENQKLRE
  TLEEYNKEFAEVKNQEVTIKALKEKIREYEQTLKNQAETIALEKEQKLQNDFAEKERKLQ
  ETQMSTTSKLEEAEHKVQSLQTALEKTRTELFDLKTKYDEETTAKADEIEMIMTDLERAN
  QRAEVAQREAETLREQLSSANHSLQLASQIQKAPDVEQAIEVLTRSSLEVELAAKEREIA
  QLVEDVQRLQASLTKLRENSASQISQLEQQLSAKNSTLKQLEEKLKGQADYEEVKKELNI
  LKSMEFAPSEGAGTQDAAKPLEVLLLEKNRSLQSENAALRISNSDLSGSARRKGKDQPES
  RRPGSLPAPPPSQLPRNPGEQASNTNGTHQFSPAGLSQDFFSSSLASPSLPLASTGKFAL
  NSLLQRQLMQSFYSKAMQEAGSTSMIFSTGPYSTNSISSQSPLQQSPDVNGMAPSPSQSE
  SAGSVSEGEEMDTAEIARQVKEQLIKHNIGQRIFGHYVLGLSQGSVSEILARPKPWNKLT
  VRGKEPFHKMKQFLSDEQNILALRSIQGRQRENPGQSLNRLFQEVPKRRNGSEGNITTRI
  RASETGSDEAIKSILEQAKRELQVQKTAEPAQPSSASGSGNSDDAIRSILQQARREMEAQ
  QAALDPALKQAPLSQSDITILTPKLLSTSPMPTVSSYPPLAISLKKPSAAPEAGASALPN
  PPALKKEAQDAPGLDPQGAADCAQGVLRQVKNEVGRSGAWKDHWWSAVQPERRNAASSEE
  AKAEETGGGKEKGSGGSGGGSQPRAERSQLQGPSSSEYWKEWPSAESPYSQSSELSLTGA
  SRSETPQNSPLPSSPIVPMSKPTKPSVPPLTPEQYEVYMYQEVDTIELTRQVKEKLAKNG
  ICQRIFGEKVLGLSQGSVSDMLSRPKPWSKLTQKGREPFIRMQLWLNGELGQGVLPVQGQ
  QQGPVLHSVTSLQDPLQQGCVSSESTPKTSASCSPAPESPMSSSESVKSLTELVQQPCPP
  IEASKDSKPPEPSDPPASDSQPTTPLPLSGHSALSIQELVAMSPELDTYGITKRVKEVLT
  DNNLGQRLFGETILGLTQGSVSDLLARPKPWHKLSLKGREPFVRMQLWLNDPNNVEKLMD
  MKRMEKKAYMKRRHSSVSDSQPCEPPSVGTEYSQGASPQPQHQLKKPRVVLAPEEKEALK
  RAYQQKPYPSPKTIEDLATQLNLKTSTVINWFHNYRSRIRRELFIEEIQAGSQGQAGASD
  SPSARSGRAAPSSEGDSCDGVEATEGPGSADTEEPKSQGEAEREEVPRPAEQTEPPPSGT
  PGPDDARDDDHEGGPVEGPGPLPSPASATATAAPAAPEDAATSAAAAPGEGPAAPSSAPP
  PSNSSSSSAPRRPSSLQSLFGLPEAAGARDSRDNPLRKKKAANLNSIIHRLEKAASREEP
  IEWEF
• Function: Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator; [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1.
• Reactome Pathway:
  Signaling by FGFR1 in disease (R-HSA-5655302)
  Signaling by cytosolic FGFR1 fusion mutants (R-HSA-1839117)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Definitive	Biomarker	[1]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[2]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[3]
Pancreatic cancer	DISJC981	Definitive	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[6]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[10]
Depression	DIS3XJ69	Strong	Biomarker	[11]
Global developmental delay with or without impaired intellectual development	DISAQVWQ	Strong	Autosomal dominant	[12]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[15]
Leiomyoma	DISLDDFN	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Altered Expression	[17]
Lung cancer	DISCM4YA	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[18]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[19]
Melanoma	DIS1RRCY	Strong	Altered Expression	[20]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[21]
Parkinson disease	DISQVHKL	Strong	Biomarker	[22]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[23]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[24]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[25]
Schizophrenia	DISSRV2N	Strong	Biomarker	[26]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[28]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[29]
Glioma	DIS5RPEH	moderate	Altered Expression	[30]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[31]
Colitis	DISAF7DD	Disputed	Genetic Variation	[32]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[33]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Altered Expression	[34]
Gastric cancer	DISXGOUK	Limited	Biomarker	[35]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[36]
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	DISD21FA	Limited	Genetic Variation	[37]
Myeloid leukaemia	DISMN944	Limited	Biomarker	[38]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[39]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[40]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Genetic Variation	[41]
Optic neuritis	DISDYCHC	Limited	Biomarker	[42]
Prostate cancer	DISF190Y	Limited	Altered Expression	[43]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[43]
Stomach cancer	DISKIJSX	Limited	Biomarker	[35]
T-cell leukaemia	DISJ6YIF	Limited	Biomarker	[44]

6 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 Homeobox protein cut-like 1 (CUX1).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Homeobox protein cut-like 1 (CUX1).	[49]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Homeobox protein cut-like 1 (CUX1).	[57]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Homeobox protein cut-like 1 (CUX1).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Homeobox protein cut-like 1 (CUX1).	[59]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Homeobox protein cut-like 1 (CUX1).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Homeobox protein cut-like 1 (CUX1).	[46]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein cut-like 1 (CUX1).	[47]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Homeobox protein cut-like 1 (CUX1).	[48]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Homeobox protein cut-like 1 (CUX1).	[50]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Homeobox protein cut-like 1 (CUX1).	[51]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Homeobox protein cut-like 1 (CUX1).	[52]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Homeobox protein cut-like 1 (CUX1).	[53]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Homeobox protein cut-like 1 (CUX1).	[54]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Homeobox protein cut-like 1 (CUX1).	[55]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein cut-like 1 (CUX1).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Homeobox protein cut-like 1 (CUX1).	[60]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Homeobox protein cut-like 1 (CUX1).	[50]

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