Details of Drug Off-Target (DOT)

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

• DOT Name: Monocarboxylate transporter 14 (SLC16A14)
• Synonyms: MCT 14; Solute carrier family 16 member 14
• Gene Name: SLC16A14
• UniProt ID: MOT14_HUMAN
• Pfam ID: PF07690
• Sequence:
  MYTSHEDIGYDFEDGPKDKKTLKPHPNIDGGWAWMMVLSSFFVHILIMGSQMALGVLNVE
  WLEEFHQSRGLTAWVSSLSMGITLIVGPFIGLFINTCGCRQTAIIGGLVNSLGWVLSAYA
  ANVHYLFITFGVAAGLGSGMAYLPAVVMVGRYFQKRRALAQGLSTTGTGFGTFLMTVLLK
  YLCAEYGWRNAMLIQGAVSLNLCVCGALMRPLSPGKNPNDPGEKDVRGLPAHSTESVKST
  GQQGRTEEKDGGLGNEETLCDLQAQECPDQAGHRKNMCALRILKTVSWLTMRVRKGFEDW
  YSGYFGTASLFTNRMFVAFIFWALFAYSSFVIPFIHLPEIVNLYNLSEQNDVFPLTSIIA
  IVHIFGKVILGVIADLPCISVWNVFLLANFTLVLSIFILPLMHTYAGLAVICALIGFSSG
  YFSLMPVVTEDLVGIEHLANAYGIIICANGISALLGPPFAGWIYDITQKYDFSFYICGLL
  YMIGILFLLIQPCIRIIEQSRRKYMDGAHV
• Function: Proton-linked monocarboxylate transporter. May catalyze the transport of monocarboxylates across the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

22 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 Monocarboxylate transporter 14 (SLC16A14).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Monocarboxylate transporter 14 (SLC16A14).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Monocarboxylate transporter 14 (SLC16A14).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Monocarboxylate transporter 14 (SLC16A14).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[9]
Fenfluramine	DM0762O	Phase 3	Fenfluramine decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Monocarboxylate transporter 14 (SLC16A14).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Monocarboxylate transporter 14 (SLC16A14).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monocarboxylate transporter 14 (SLC16A14).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Monocarboxylate transporter 14 (SLC16A14).	[19]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Monocarboxylate transporter 14 (SLC16A14).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] 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.
• [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] 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.
• [12] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [13] Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
• [14] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.