Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT04XNOU)

• DOT Name: Nuclear receptor corepressor 1 (NCOR1)
• Synonyms: N-CoR; N-CoR1
• Gene Name: NCOR1
• Related Disease:
  Abdominal aortic aneurysm
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Autism spectrum disorder
  B-cell lymphoma
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Endometriosis
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hypothyroidism
  Leiomyoma
  leukaemia
  Leukemia
  Liver cancer
  Lung adenocarcinoma
  Lung neoplasm
  Metabolic disorder
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Pervasive developmental disorder
  Polycystic ovarian syndrome
  Progressive multifocal leukoencephalopathy
  Prostate neoplasm
  Rheumatoid arthritis
  Uterine fibroids
  Anxiety disorder
  Ductal breast carcinoma in situ
  Gastrointestinal stromal tumour
  Metastatic malignant neoplasm
  Promyelocytic leukaemia
  Prostate carcinoma
  Generalized resistance to thyroid hormone
  Invasive breast carcinoma
  Prostate cancer
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: NCOR1_HUMAN
• PDB ID: 2EQR; 3H52; 3KMZ; 3N00; 4MDD; 4WVD; 6ONI; 6WMQ; 6WMS; 6XXS; 6XYX; 6XZZ; 6Y17; 6ZBU; 8AS9; 8D8I; 8DKN; 8DKV
• Pfam ID: PF15784 ; PF00249
• Sequence:
  MSSSGYPPNQGAFSTEQSRYPPHSVQYTFPNTRHQQEFAVPDYRSSHLEVSQASQLLQQQ
  QQQQLRRRPSLLSEFHPGSDRPQERRTSYEPFHPGPSPVDHDSLESKRPRLEQVSDSHFQ
  RVSAAVLPLVHPLPEGLRASADAKKDPAFGGKHEAPSSPISGQPCGDDQNASPSKLSKEE
  LIQSMDRVDREIAKVEQQILKLKKKQQQLEEEAAKPPEPEKPVSPPPVEQKHRSIVQIIY
  DENRKKAEEAHKIFEGLGPKVELPLYNQPSDTKVYHENIKTNQVMRKKLILFFKRRNHAR
  KQREQKICQRYDQLMEAWEKKVDRIENNPRRKAKESKTREYYEKQFPEIRKQREQQERFQ
  RVGQRGAGLSATIARSEHEISEIIDGLSEQENNEKQMRQLSVIPPMMFDAEQRRVKFINM
  NGLMEDPMKVYKDRQFMNVWTDHEKEIFKDKFIQHPKNFGLIASYLERKSVPDCVLYYYL
  TKKNENYKALVRRNYGKRRGRNQQIARPSQEEKVEEKEEDKAEKTEKKEEEKKDEEEKDE
  KEDSKENTKEKDKIDGTAEETEEREQATPRGRKTANSQGRRKGRITRSMTNEAAAASAAA
  AAATEEPPPPLPPPPEPISTEPVETSRWTEEEMEVAKKGLVEHGRNWAAIAKMVGTKSEA
  QCKNFYFNYKRRHNLDNLLQQHKQKTSRKPREERDVSQCESVASTVSAQEDEDIEASNEE
  ENPEDSEVEAVKPSEDSPENATSRGNTEPAVELEPTTETAPSTSPSLAVPSTKPAEDESV
  ETQVNDSISAETAEQMDVDQQEHSAEEGSVCDPPPATKADSVDVEVRVPENHASKVEGDN
  TKERDLDRASEKVEPRDEDLVVAQQINAQRPEPQSDNDSSATCSADEDVDGEPERQRMFP
  MDSKPSLLNPTGSILVSSPLKPNPLDLPQLQHRAAVIPPMVSCTPCNIPIGTPVSGYALY
  QRHIKAMHESALLEEQRQRQEQIDLECRSSTSPCGTSKSPNREWEVLQPAPHQVITNLPE
  GVRLPTTRPTRPPPPLIPSSKTTVASEKPSFIMGGSISQGTPGTYLTSHNQASYTQETPK
  PSVGSISLGLPRQQESAKSATLPYIKQEEFSPRSQNSQPEGLLVRAQHEGVVRGTAGAIQ
  EGSITRGTPTSKISVESIPSLRGSITQGTPALPQTGIPTEALVKGSISRMPIEDSSPEKG
  REEAASKGHVIYEGKSGHILSYDNIKNAREGTRSPRTAHEISLKRSYESVEGNIKQGMSM
  RESPVSAPLEGLICRALPRGSPHSDLKERTVLSGSIMQGTPRATTESFEDGLKYPKQIKR
  ESPPIRAFEGAITKGKPYDGITTIKEMGRSIHEIPRQDILTQESRKTPEVVQSTRPIIEG
  SISQGTPIKFDNNSGQSAIKHNVKSLITGPSKLSRGMPPLEIVPENIKVVERGKYEDVKA
  GETVRSRHTSVVSSGPSVLRSTLHEAPKAQLSPGIYDDTSARRTPVSYQNTMSRGSPMMN
  RTSDVTISSNKSTNHERKSTLTPTQRESIPAKSPVPGVDPVVSHSPFDPHHRGSTAGEVY
  RSHLPTHLDPAMPFHRALDPAAAAYLFQRQLSPTPGYPSQYQLYAMENTRQTILNDYITS
  QQMQVNLRPDVARGLSPREQPLGLPYPATRGIIDLTNMPPTILVPHPGGTSTPPMDRITY
  IPGTQITFPPRPYNSASMSPGHPTHLAAAASAEREREREREKERERERIAAASSDLYLRP
  GSEQPGRPGSHGYVRSPSPSVRTQETMLQQRPSVFQGTNGTSVITPLDPTAQLRIMPLPA
  GGPSISQGLPASRYNTAADALAALVDAAASAPQMDVSKTKESKHEAARLEENLRSRSAAV
  SEQQQLEQKTLEVEKRSVQCLYTSSAFPSGKPQPHSSVVYSEAGKDKGPPPKSRYEEELR
  TRGKTTITAANFIDVIITRQIASDKDARERGSQSSDSSSSLSSHRYETPSDAIEVISPAS
  SPAPPQEKLQTYQPEVVKANQAENDPTRQYEGPLHHYRPQQESPSPQQQLPPSSQAEGMG
  QVPRTHRLITLADHICQIITQDFARNQVSSQTPQQPPTSTFQNSPSALVSTPVRTKTSNR
  YSPESQAQSVHHQRPGSRVSPENLVDKSRGSRPGKSPERSHVSSEPYEPISPPQVPVVHE
  KQDSLLLLSQRGAEPAEQRNDARSPGSISYLPSFFTKLENTSPMVKSKKQEIFRKLNSSG
  GGDSDMAAAQPGTEIFNLPAVTTSGSVSSRGHSFADPASNLGLEDIIRKALMGSFDDKVE
  DHGVVMSQPMGVVPGTANTSVVTSGETRREEGDPSPHSGGVCKPKLISKSNSRKSKSPIP
  GQGYLGTERPSSVSSVHSEGDYHRQTPGWAWEDRPSSTGSTQFPYNPLTMRMLSSTPPTP
  IACAPSAVNQAAPHQQNRIWEREPAPLLSAQYETLSDSDD
• Function: Mediates transcriptional repression by certain nuclear receptors. Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation. Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression. The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  TGF-beta sig.ling pathway (hsa04350)
  Thyroid hormone sig.ling pathway (hsa04919)
  Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway:
  NR1D1 (REV-ERBA) represses gene expression (R-HSA-1368071)
  PPARA activates gene expression (R-HSA-1989781)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Downregulation of SMAD2/3 (R-HSA-2173795)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  HDACs deacetylate histones (R-HSA-3214815)
  Notch-HLH transcription pathway (R-HSA-350054)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Nuclear Receptor transcription pathway (R-HSA-383280)
  Regulation of lipid metabolism by PPARalpha (R-HSA-400206)
  Circadian Clock (R-HSA-400253)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  Loss of MECP2 binding ability to the NCoR/SMRT complex (R-HSA-9022537)
  Regulation of MECP2 expression and activity (R-HSA-9022692)
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  HCMV Early Events (R-HSA-9609690)
  NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis (R-HSA-9623433)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme signaling (R-HSA-9707616)
  Nuclear signaling by ERBB4 (R-HSA-1251985)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[1]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[3]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[6]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[6]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[7]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[8]
B-cell neoplasm	DISVY326	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[13]
Endometriosis	DISX1AG8	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[17]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[18]
leukaemia	DISS7D1V	Strong	Genetic Variation	[19]
Leukemia	DISNAKFL	Strong	Genetic Variation	[19]
Liver cancer	DISDE4BI	Strong	Biomarker	[20]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[11]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[11]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Obesity	DIS47Y1K	Strong	Biomarker	[21]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[7]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[23]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Altered Expression	[24]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[25]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[26]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[18]
Anxiety disorder	DISBI2BT	moderate	Biomarker	[27]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[28]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Altered Expression	[29]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[5]
Promyelocytic leukaemia	DISYGG13	moderate	Biomarker	[30]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[5]
Generalized resistance to thyroid hormone	DIS4TOK0	Limited	Biomarker	[31]
Invasive breast carcinoma	DISANYTW	Limited	Altered Expression	[32]
Prostate cancer	DISF190Y	Limited	Biomarker	[25]
Transitional cell carcinoma	DISWVVDR	Limited	Biomarker	[33]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[33]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Nuclear receptor corepressor 1 (NCOR1).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Nuclear receptor corepressor 1 (NCOR1).	[35]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Nuclear receptor corepressor 1 (NCOR1).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nuclear receptor corepressor 1 (NCOR1).	[47]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear receptor corepressor 1 (NCOR1).	[48]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nuclear receptor corepressor 1 (NCOR1).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Nuclear receptor corepressor 1 (NCOR1).	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nuclear receptor corepressor 1 (NCOR1).	[42]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Nuclear receptor corepressor 1 (NCOR1).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the activity of Nuclear receptor corepressor 1 (NCOR1).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[41]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nuclear receptor corepressor 1 (NCOR1).	[43]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Nuclear receptor corepressor 1 (NCOR1).	[40]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Nuclear receptor corepressor 1 (NCOR1).	[44]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[45]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Nuclear receptor corepressor 1 (NCOR1).	[46]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear receptor corepressor 1 (NCOR1).	[49]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Nuclear receptor corepressor 1 (NCOR1).	[52]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the activity of Nuclear receptor corepressor 1 (NCOR1).	[15]

References

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