Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT47IF19)

• DOT Name: Small integral membrane protein 14 (SMIM14)
• Gene Name: SMIM14
• UniProt ID: SIM14_HUMAN
• Pfam ID: PF11027
• Sequence:
  MAEGGFDPCECVCSHEHAMRRLINLLRQSQSYCTDTECLQELPGPSGDNGISVTMILVAW
  MVIALILFLLRPPNLRGSSLPGKPTSPHNGQDPPAPPVD

Molecular Interaction Atlas (MIA) of This DOT

32 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 Small integral membrane protein 14 (SMIM14).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Small integral membrane protein 14 (SMIM14).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Small integral membrane protein 14 (SMIM14).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Small integral membrane protein 14 (SMIM14).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Small integral membrane protein 14 (SMIM14).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small integral membrane protein 14 (SMIM14).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Small integral membrane protein 14 (SMIM14).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Small integral membrane protein 14 (SMIM14).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Small integral membrane protein 14 (SMIM14).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Small integral membrane protein 14 (SMIM14).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Small integral membrane protein 14 (SMIM14).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Small integral membrane protein 14 (SMIM14).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Small integral membrane protein 14 (SMIM14).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Small integral membrane protein 14 (SMIM14).	[12]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Small integral membrane protein 14 (SMIM14).	[11]
Docetaxel	DMDI269	Approved	Docetaxel decreases the expression of Small integral membrane protein 14 (SMIM14).	[11]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Small integral membrane protein 14 (SMIM14).	[13]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of Small integral membrane protein 14 (SMIM14).	[11]
Bleomycin	DMNER5S	Approved	Bleomycin decreases the expression of Small integral membrane protein 14 (SMIM14).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Small integral membrane protein 14 (SMIM14).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Small integral membrane protein 14 (SMIM14).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Small integral membrane protein 14 (SMIM14).	[6]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Small integral membrane protein 14 (SMIM14).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Small integral membrane protein 14 (SMIM14).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Small integral membrane protein 14 (SMIM14).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small integral membrane protein 14 (SMIM14).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Small integral membrane protein 14 (SMIM14).	[20]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Small integral membrane protein 14 (SMIM14).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Small integral membrane protein 14 (SMIM14).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Small integral membrane protein 14 (SMIM14).	[22]
Manganese	DMKT129	Investigative	Manganese increases the expression of Small integral membrane protein 14 (SMIM14).	[23]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Small integral membrane protein 14 (SMIM14).	[11]

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 HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 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.
• [4] 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.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] 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.
• [10] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [11] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [17] 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.
• [18] 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.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [21] 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.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [23] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.