Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI9JUWA)

• DOT Name: Nuclear protein MDM1 (MDM1)
• Gene Name: MDM1
• Related Disease: Schizophrenia
• UniProt ID: MDM1_HUMAN
• Pfam ID: PF15501
• Sequence:
  MPVRFKGLSEYQRNFLWKKSYLSESCNSSVGRKYPWAGLRSDQLGITKEPSFISKRRVPY
  HDPQISKSLEWNGAISESNVVASPEPEAPETPKSQEAEQKDVTQERVHSLEASRVPKRTR
  SHSADSRAEGASDVENNEGVTNHTPVNENVELEHSTKVLSENVDNGLDRLLRKKAGLTVV
  PSYNALRNSEYQRQFVWKTSKETAPAFAANQVFHNKSQFVPPFKGNSVIHETEYKRNFKG
  LSPVKEPKLRNDLRENRNLETVSPERKSNKIDDRLKLEAEMELKDLHQPKRKLTPWKHQR
  LGKVNSEYRAKFLSPAQYLYKAGAWTHVKGNMPNQVKELREKAEFYRKRVQGTHFSRDHL
  NQILSDSNCCWDVSSTTSSEGTVSSNIRALDLAGDPTSHKTLQKCPSTEPEEKGNIVEEQ
  PQKNTTEKLGVSAPTIPVRRRLAWDTENTSEDVQKQPGEKEEEDDNEEEGDRKTGKQAFM
  GEQEKLDVREKSKADKMKEGSDSSVSSEKGGRLPTPKLRELGGIQRTHHDLTTPAVGGAV
  LVSPSKMKPPAPEQRKRMTSQDCLETSKNDFTKKESRAVSLLTSPAAGIKTVDPLPLRED
  SEDNIHKFAEATLPVSKIPKYPTNPPGQLPSPPHVPSYWHPSRRIQGSLRDPEFQHNVGK
  ARMNNLQLPQHEAFNDEDEDRLSEISARSAASSLRAFQTLARAKKRKENFWGKT
• Function: Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nuclear protein MDM1 (MDM1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear protein MDM1 (MDM1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear protein MDM1 (MDM1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear protein MDM1 (MDM1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear protein MDM1 (MDM1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nuclear protein MDM1 (MDM1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nuclear protein MDM1 (MDM1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Nuclear protein MDM1 (MDM1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nuclear protein MDM1 (MDM1).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nuclear protein MDM1 (MDM1).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Nuclear protein MDM1 (MDM1).	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Nuclear protein MDM1 (MDM1).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Nuclear protein MDM1 (MDM1).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Nuclear protein MDM1 (MDM1).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Nuclear protein MDM1 (MDM1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear protein MDM1 (MDM1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Nuclear protein MDM1 (MDM1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nuclear protein MDM1 (MDM1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear protein MDM1 (MDM1).	[18]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] 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.
• [12] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [13] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [14] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [15] 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.
• [16] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.