Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDBU4F3)

• DOT Name: Chromodomain-helicase-DNA-binding protein 3 (CHD3)
• Synonyms: CHD-3; EC 3.6.4.12; ATP-dependent helicase CHD3; Mi-2 autoantigen 240 kDa protein; Mi2-alpha; Zinc finger helicase; hZFH
• Gene Name: CHD3
• Related Disease:
  Snijders Blok-Campeau syndrome
  X-linked intellectual disability
  Breast cancer
  Breast carcinoma
  Familial prostate carcinoma
  Idiopathic inflammatory myopathy
  Intellectual disability
  Megalencephaly
  Neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Prostate neoplasm
  Sezary syndrome
  Stroke
• UniProt ID: CHD3_HUMAN
• EC Number: 3.6.4.12
• Pfam ID: PF08074 ; PF06461 ; PF08073 ; PF00385 ; PF06465 ; PF00271 ; PF00628 ; PF00176
• Sequence:
  MKAADTVILWARSKNDQLRISFPPGLCWGDRMPDKDDIRLLPSALGVKKRKRGPKKQKEN
  KPGKPRKRKKRDSEEEFGSERDEYREKSESGGSEYGTGPGRKRRRKHREKKEKKTKRRKK
  GEGDGGQKQVEQKSSATLLLTWGLEDVEHVFSEEDYHTLTNYKAFSQFMRPLIAKKNPKI
  PMSKMMTILGAKWREFSANNPFKGSAAAVAAAAAAAAAAVAEQVSAAVSSATPIAPSGPP
  ALPPPPAADIQPPPIRRAKTKEGKGPGHKRRSKSPRVPDGRKKLRGKKMAPLKIKLGLLG
  GKRKKGGSYVFQSDEGPEPEAEESDLDSGSVHSASGRPDGPVRTKKLKRGRPGRKKKKVL
  GCPAVAGEEEVDGYETDHQDYCEVCQQGGEIILCDTCPRAYHLVCLDPELDRAPEGKWSC
  PHCEKEGVQWEAKEEEEEYEEEGEEEGEKEEEDDHMEYCRVCKDGGELLCCDACISSYHI
  HCLNPPLPDIPNGEWLCPRCTCPVLKGRVQKILHWRWGEPPVAVPAPQQADGNPDVPPPR
  PLQGRSEREFFVKWVGLSYWHCSWAKELQLEIFHLVMYRNYQRKNDMDEPPPLDYGSGED
  DGKSDKRKVKDPHYAEMEEKYYRFGIKPEWMTVHRIINHSVDKKGNYHYLVKWRDLPYDQ
  STWEEDEMNIPEYEEHKQSYWRHRELIMGEDPAQPRKYKKKKKELQGDGPPSSPTNDPTV
  KYETQPRFITATGGTLHMYQLEGLNWLRFSWAQGTDTILADEMGLGKTIQTIVFLYSLYK
  EGHTKGPFLVSAPLSTIINWEREFQMWAPKFYVVTYTGDKDSRAIIRENEFSFEDNAIKG
  GKKAFKMKREAQVKFHVLLTSYELITIDQAALGSIRWACLVVDEAHRLKNNQSKFFRVLN
  GYKIDHKLLLTGTPLQNNLEELFHLLNFLTPERFNNLEGFLEEFADISKEDQIKKLHDLL
  GPHMLRRLKADVFKNMPAKTELIVRVELSPMQKKYYKYILTRNFEALNSRGGGNQVSLLN
  IMMDLKKCCNHPYLFPVAAMESPKLPSGAYEGGALIKSSGKLMLLQKMLRKLKEQGHRVL
  IFSQMTKMLDLLEDFLDYEGYKYERIDGGITGALRQEAIDRFNAPGAQQFCFLLSTRAGG
  LGINLATADTVIIFDSDWNPHNDIQAFSRAHRIGQANKVMIYRFVTRASVEERITQVAKR
  KMMLTHLVVRPGLGSKAGSMSKQELDDILKFGTEELFKDENEGENKEEDSSVIHYDNEAI
  ARLLDRNQDATEDTDVQNMNEYLSSFKVAQYVVREEDKIEEIEREIIKQEENVDPDYWEK
  LLRHHYEQQQEDLARNLGKGKRVRKQVNYNDAAQEDQDNQSEYSVGSEEEDEDFDERPEG
  RRQSKRQLRNEKDKPLPPLLARVGGNIEVLGFNTRQRKAFLNAVMRWGMPPQDAFTTQWL
  VRDLRGKTEKEFKAYVSLFMRHLCEPGADGSETFADGVPREGLSRQQVLTRIGVMSLVKK
  KVQEFEHINGRWSMPELMPDPSADSKRSSRASSPTKTSPTTPEASATNSPCTSKPATPAP
  SEKGEGIRTPLEKEEAENQEEKPEKNSRIGEKMETEADAPSPAPSLGERLEPRKIPLEDE
  VPGVPGEMEPEPGYRGDREKSATESTPGERGEEKPLDGQEHRERPEGETGDLGKREDVKG
  DRELRPGPRDEPRSNGRREEKTEKPRFMFNIADGGFTELHTLWQNEERAAISSGKLNEIW
  HRRHDYWLLAGIVLHGYARWQDIQNDAQFAIINEPFKTEANKGNFLEMKNKFLARRFKLL
  EQALVIEEQLRRAAYLNLSQEPAHPAMALHARFAEAECLAESHQHLSKESLAGNKPANAV
  LHKVLNQLEELLSDMKADVTRLPATLSRIPPIAARLQMSERSILSRLASKGTEPHPTPAY
  PPGPYATPPGYGAAFSAAPVGALAAAGANYSQMPAGSFITAATNGPPVLVKKEKEMVGAL
  VSDGLDRKEPRAGEVICIDD
• Function: ATP-dependent helicase that binds and distorts nucleosomal DNA. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Involved in transcriptional repression as part of the NuRD complex. Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway:
  ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  Regulation of TP53 Activity through Acetylation (R-HSA-6804758)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Potential therapeutics for SARS (R-HSA-9679191)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Snijders Blok-Campeau syndrome	DISH0AG5	Definitive	Autosomal dominant	[1]
X-linked intellectual disability	DISYJBY3	Definitive	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[4]
Idiopathic inflammatory myopathy	DISGB1BZ	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	Strong	Biomarker	[6]
Megalencephaly	DISYW5SV	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Pancreatic cancer	DISJC981	Strong	ModifyingMutation	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[9]
Sezary syndrome	DISFMTC7	Strong	Biomarker	[10]
Stroke	DISX6UHX	moderate	Genetic Variation	[11]

6 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 Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[17]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid affects the phosphorylation of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[25]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[18]
Selenium	DM25CGV	Approved	Selenium increases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[24]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Chromodomain-helicase-DNA-binding protein 3 (CHD3).	[20]

References

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• [2] Mutational analysis of the ATRX gene by DGGE: a powerful diagnostic approach for the ATRX syndrome.Hum Mutat. 2003 May;21(5):529-34. doi: 10.1002/humu.10183.
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• [4] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [5] Autoantibodies to Mi-2 alpha and Mi-2 beta in patients with idiopathic inflammatory myopathy.Rheumatology (Oxford). 2019 Sep 1;58(9):1655-1661. doi: 10.1093/rheumatology/kez092.
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• [11] Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans.Stroke. 2015 Aug;46(8):2063-8. doi: 10.1161/STROKEAHA.115.009044. Epub 2015 Jun 18.
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• [19] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [20] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
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• [22] 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.
• [23] 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.
• [24] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
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• [26] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.