Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS87F3H)

• DOT Name: Meiotic nuclear division protein 1 homolog (MND1)
• Gene Name: MND1
• UniProt ID: MND1_HUMAN
• Pfam ID: PF18517 ; PF03962
• Sequence:
  MSKKKGLSAEEKRTRMMEIFSETKDVFQLKDLEKIAPKEKGITAMSVKEVLQSLVDDGMV
  DCERIGTSNYYWAFPSKALHARKHKLEVLESQLSEGSQKHASLQKSIEKAKIGRCETEER
  TRLAKELSSLRDQREQLKAEVEKYKDCDPQVVEEIRQANKVAKEAANRWTDNIFAIKSWA
  KRKFGFEENKIDRTFGIPEDFDYID
• Function: Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis. Stimulates both DMC1- and RAD51-mediated homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.
• Reactome Pathway: Meiotic recombination (R-HSA-912446)

Molecular Interaction Atlas (MIA) of This DOT

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 Meiotic nuclear division protein 1 homolog (MND1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[11]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[12]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[13]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Meiotic nuclear division protein 1 homolog (MND1).	[20]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [12] 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.
• [13] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [14] 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.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] 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.
• [18] 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.
• [19] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [20] 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.