Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWN3S47)

• DOT Name: Nuclear envelope integral membrane protein 1 (NEMP1)
• Gene Name: NEMP1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Acute myelogenous leukaemia
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: NEMP1_HUMAN
• Pfam ID: PF10225
• Sequence:
  MAGGMKVAVSPAVGPGPWGSGVGGGGTVRLLLILSGCLVYGTAETDVNVVMLQESQVCEK
  RASQQFCYTNVLIPKWHDIWTRIQIRVNSSRLVRVTQVENEEKLKELEQFSIWNFFSSFL
  KEKLNDTYVNVGLYSTKTCLKVEIIEKDTKYSVIVIRRFDPKLFLVFLLGLMLFFCGDLL
  SRSQIFYYSTGMTVGIVASLLIIIFILSKFMPKKSPIYVILVGGWSFSLYLIQLVFKNLQ
  EIWRCYWQYLLSYVLTVGFMSFAVCYKYGPLENERSINLLTWTLQLMGLCFMYSGIQIPH
  IALAIIIIALCTKNLEHPIQWLYITCRKVCKGAEKPVPPRLLTEEEYRIQGEVETRKALE
  ELREFCNSPDCSAWKTVSRIQSPKRFADFVEGSSHLTPNEVSVHEQEYGLGSIIAQDEIY
  EEASSEEEDSYSRCPAITQNNFLT
• Function: Together with EMD, contributes to nuclear envelope stiffness in germ cells. Required for female fertility. Essential for normal erythropoiesis. Required for efficient nuclear envelope opening and enucleation during the late stages of erythroblast maturation.

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]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Thyroid cancer	DIS3VLDH	Disputed	Biomarker	[3]
Thyroid gland carcinoma	DISMNGZ0	Disputed	Biomarker	[3]
Thyroid tumor	DISLVKMD	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[13]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nuclear envelope integral membrane protein 1 (NEMP1).	[8]

References

• [1] NEMP1 Promotes Tamoxifen Resistance in Breast Cancer Cells.Biochem Genet. 2019 Dec;57(6):813-826. doi: 10.1007/s10528-019-09926-0. Epub 2019 May 11.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Gene master regulators of papillary and anaplastic thyroid cancers.Oncotarget. 2017 Dec 19;9(2):2410-2424. doi: 10.18632/oncotarget.23417. eCollection 2018 Jan 5.
• [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] 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.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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] 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.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] 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.
• [14] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.