Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBWDA4E)

• DOT Name: Histone H1.10 (H1-10)
• Synonyms: Histone H1x
• Gene Name: H1-10
• Related Disease:
  Lung adenocarcinoma
  Neuroendocrine neoplasm
• UniProt ID: H1X_HUMAN
• PDB ID: 2LSO; 6L9Z; 7K60; 7K63; 7XX7
• Pfam ID: PF00538
• Sequence:
  MSVELEEALPVTTAEGMAKKVTKAGGSAALSPSKKRKNSKKKNQPGKYSQLVVETIRRLG
  ERNGSSLAKIYTEAKKVPWFDQQNGRTYLKYSIKALVQNDTLLQVKGTGANGSFKLNRKK
  LEGGGERRGAPAAATAPAPTAHKAKKAAPGAAGSRRADKKPARGQKPEQRSHKKGAGAKK
  DKGGKAKKTAAAGGKKVKKAAKPSVPKVPKGRK
• Function: Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures.
• Tissue Specificity: Expressed ubiquitously.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Neuroendocrine neoplasm	DISNPLOO	Limited	Altered Expression	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Histone H1.10 (H1-10) affects the response to substance of Methotrexate.	[24]

21 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 Histone H1.10 (H1-10).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Histone H1.10 (H1-10).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Histone H1.10 (H1-10).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H1.10 (H1-10).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone H1.10 (H1-10).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone H1.10 (H1-10).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H1.10 (H1-10).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone H1.10 (H1-10).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone H1.10 (H1-10).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Histone H1.10 (H1-10).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone H1.10 (H1-10).	[13]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Histone H1.10 (H1-10).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone H1.10 (H1-10).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Histone H1.10 (H1-10).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Histone H1.10 (H1-10).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Histone H1.10 (H1-10).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone H1.10 (H1-10).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H1.10 (H1-10).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Histone H1.10 (H1-10).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H1.10 (H1-10).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Histone H1.10 (H1-10).	[23]

References

• [1] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [2] Histone H1x is highly expressed in human neuroendocrine cells and tumours.BMC Cancer. 2008 Dec 24;8:388. doi: 10.1186/1471-2407-8-388.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [17] Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts. Anticancer Drugs. 2009 Sep;20(8):682-92.
• [18] BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
• [19] 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.
• [20] Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells. Environ Res. 2006 Jan;100(1):86-92.
• [21] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [22] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] 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.