Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAO7Z87)

• DOT Name: Isochorismatase domain-containing protein 1 (ISOC1)
• Gene Name: ISOC1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Neoplasm
  Advanced cancer
  Pancreatic cancer
• UniProt ID: ISOC1_HUMAN
• Pfam ID: PF00857
• Sequence:
  MAAAEPAVLALPNSGAGGAGAPSGTVPVLFCFSVFARPSSVPHGAGYELLIQKFLSLYGD
  QIDMHRKFVVQLFAEEWGQYVDLPKGFAVSERCKVRLVPLQIQLTTLGNLTPSSTVFFCC
  DMQERFRPAIKYFGDIISVGQRLLQGARILGIPVIVTEQYPKGLGSTVQEIDLTGVKLVL
  PKTKFSMVLPEVEAALAEIPGVRSVVLFGVETHVCIQQTALELVGRGVEVHIVADATSSR
  SMMDRMFALERLARTGIIVTTSEAVLLQLVADKDHPKFKEIQNLIKASAPESGLLSKV

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[1]
Pancreatic cancer	DISJC981	Limited	Biomarker	[1]

1 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 Isochorismatase domain-containing protein 1 (ISOC1).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Isochorismatase domain-containing protein 1 (ISOC1).	[16]

References

• [1] Knockdown of ISOC1 suppresses cell proliferation in pancreatic cancer in vitro.Oncol Lett. 2019 May;17(5):4263-4270. doi: 10.3892/ol.2019.10082. Epub 2019 Feb 28.
• [2] Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3 pathway.Carcinogenesis. 2020 Aug 12;41(8):1123-1133. doi: 10.1093/carcin/bgz188.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [13] 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.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.