Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXOS97C)

• DOT Name: Condensin complex subunit 2 (NCAPH)
• Synonyms: Barren homolog protein 1; Chromosome-associated protein H; hCAP-H; Non-SMC condensin I complex subunit H; XCAP-H homolog
• Gene Name: NCAPH
• Related Disease:
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Prostate cancer
  Prostate carcinoma
  Chromosomal disorder
  Pancreatic cancer
  Isolated congenital microcephaly
  Microcephaly 23, primary, autosomal recessive
• UniProt ID: CND2_HUMAN
• PDB ID: 6IGX
• Pfam ID: PF05786
• Sequence:
  MGPPGPALPATMNNSSSETRGHPHSASSPSERVFPMPLPRKAPLNIPGTPVLEDFPQNDD
  EKERLQRRRSRVFDLQFSTDSPRLLASPSSRSIDISATIPKFTNTQITEHYSTCIKLSTE
  NKITTKNAFGLHLIDFMSEILKQKDTEPTNFKVAAGTLDASTKIYAVRVDAVHADVYRVL
  GGLGKDAPSLEEVEGHVADGSATEMGTTKKAVKPKKKHLHRTIEQNINNLNVSEADRKCE
  IDPMFQKTAASFDECSTAGVFLSTLHCQDYRSELLFPSDVQTLSTGEPLELPELGCVEMT
  DLKAPLQQCAEDRQICPSLAGFQFTQWDSETHNESVSALVDKFKKNDQVFDINAEVDESD
  CGDFPDGSLGDDFDANDEPDHTAVGDHEEFRSWKEPCQVQSCQEEMISLGDGDIRTMCPL
  LSMKPGEYSYFSPRTMSMWAGPDHWRFRPRRKQDAPSQSENKKKSTKKDFEIDFEDDIDF
  DVYFRKTKAATILTKSTLENQNWRATTLPTDFNYNVDTLVQLHLKPGTRLLKMAQGHRVE
  TEHYEEIEDYDYNNPNDTSNFCPGLQAADSDDEDLDDLFVGPVGNSDLSPYPCHPPKTAQ
  QNGDTPEAQGLDITTYGESNLVAEPQKVNKIEIHYAKTAKKMDMKKLKQSMWSLLTALSG
  KEADAEANHREAGKEAALAEVADEKMLSGLTKDLQRSLPPVMAQNLSIPLAFACLLHLAN
  EKNLKLEGTEDLSDVLVRQGD
• Function: Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size.
• Tissue Specificity: Widely expressed at low level. Expressed in proliferating cells.
• Reactome Pathway: Condensation of Prometaphase Chromosomes (R-HSA-2514853)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Chromosomal disorder	DISM5BB5	moderate	Biomarker	[4]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[4]
Isolated congenital microcephaly	DISUXHZ6	Limited	Biomarker	[5]
Microcephaly 23, primary, autosomal recessive	DIS95ZI9	Limited	Unknown	[6]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Condensin complex subunit 2 (NCAPH) affects the response to substance of Topotecan.	[35]
Vinblastine	DM5TVS3	Approved	Condensin complex subunit 2 (NCAPH) affects the response to substance of Vinblastine.	[35]

31 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 Condensin complex subunit 2 (NCAPH).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Condensin complex subunit 2 (NCAPH).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Condensin complex subunit 2 (NCAPH).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Condensin complex subunit 2 (NCAPH).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Condensin complex subunit 2 (NCAPH).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Condensin complex subunit 2 (NCAPH).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Condensin complex subunit 2 (NCAPH).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Condensin complex subunit 2 (NCAPH).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Condensin complex subunit 2 (NCAPH).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Condensin complex subunit 2 (NCAPH).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Condensin complex subunit 2 (NCAPH).	[16]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Condensin complex subunit 2 (NCAPH).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Condensin complex subunit 2 (NCAPH).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Condensin complex subunit 2 (NCAPH).	[19]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Condensin complex subunit 2 (NCAPH).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Condensin complex subunit 2 (NCAPH).	[20]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Condensin complex subunit 2 (NCAPH).	[21]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Condensin complex subunit 2 (NCAPH).	[22]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Condensin complex subunit 2 (NCAPH).	[23]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Condensin complex subunit 2 (NCAPH).	[24]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Condensin complex subunit 2 (NCAPH).	[25]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Condensin complex subunit 2 (NCAPH).	[24]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Condensin complex subunit 2 (NCAPH).	[13]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Condensin complex subunit 2 (NCAPH).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Condensin complex subunit 2 (NCAPH).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Condensin complex subunit 2 (NCAPH).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Condensin complex subunit 2 (NCAPH).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Condensin complex subunit 2 (NCAPH).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Condensin complex subunit 2 (NCAPH).	[32]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Condensin complex subunit 2 (NCAPH).	[33]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Condensin complex subunit 2 (NCAPH).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of Condensin complex subunit 2 (NCAPH).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Condensin complex subunit 2 (NCAPH).	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Condensin complex subunit 2 (NCAPH).	[30]

References

• [1] NCAPH plays important roles in human colon cancer.Cell Death Dis. 2017 Mar 16;8(3):e2680. doi: 10.1038/cddis.2017.88.
• [2] Non-SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma.Mol Carcinog. 2019 Dec;58(12):2266-2275. doi: 10.1002/mc.23114. Epub 2019 Sep 15.
• [3] Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer.Oncol Lett. 2019 Jun;17(6):5768-5776. doi: 10.3892/ol.2019.10260. Epub 2019 Apr 17.
• [4] Non-SMC condensin I complex subunit H mediates mature chromosome condensation and DNA damage in pancreatic cancer cells.Sci Rep. 2019 Nov 29;9(1):17889. doi: 10.1038/s41598-019-54478-3.
• [5] Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis. Genes Dev. 2016 Oct 1;30(19):2158-2172. doi: 10.1101/gad.286351.116. Epub 2016 Oct 13.
• [6] A de novo 7.9 Mb deletion in 22q13.2qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. Eur J Med Genet. 2010 Sep-Oct;53(5):329-32. doi: 10.1016/j.ejmg.2010.06.004. Epub 2010 Jun 9.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion. Toxicol In Vitro. 2009 Apr;23(3):486-99.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [19] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [22] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [23] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [24] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [25] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [26] Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling. J Proteome Res. 2014 Dec 5;13(12):5734-42. doi: 10.1021/pr500714a. Epub 2014 Oct 29.
• [27] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [28] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [29] 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.
• [30] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [31] 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.
• [32] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [33] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [34] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [35] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.