Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH70529)

• DOT Name: Monocarboxylate transporter 10 (SLC16A10)
• Synonyms: MCT 10; Aromatic amino acid transporter 1; Solute carrier family 16 member 10; T-type amino acid transporter 1
• Gene Name: SLC16A10
• UniProt ID: MOT10_HUMAN
• Pfam ID: PF07690
• Sequence:
  MVLSQEEPDSARGTSEAQPLGPAPTGAAPPPGPGPSDSPEAAVEKVEVELAGPATAEPHE
  PPEPPEGGWGWLVMLAAMWCNGSVFGIQNACGVLFVSMLETFGSKDDDKMVFKTAWVGSL
  SMGMIFFCCPIVSVFTDLFGCRKTAVVGAAVGFVGLMSSSFVSSIEPLYLTYGIIFACGC
  SFAYQPSLVILGHYFKKRLGLVNGIVTAGSSVFTILLPLLLRVLIDSVGLFYTLRVLCIF
  MFVLFLAGFTYRPLATSTKDKESGGSGSSLFSRKKFSPPKKIFNFAIFKVTAYAVWAVGI
  PLALFGYFVPYVHLMKHVNERFQDEKNKEVVLMCIGVTSGVGRLLFGRIADYVPGVKKVY
  LQVLSFFFIGLMSMMIPLCSIFGALIAVCLIMGLFDGCFISIMAPIAFELVGAQDVSQAI
  GFLLGFMSIPMTVGPPIAGLLRDKLGSYDVAFYLAGVPPLIGGAVLCFIPWIHSKKQREI
  SKTTGKEKMEKMLENQNSLLSSSSGMFKKESDSII
• Function: Sodium- and proton-independent thyroid hormones and aromatic acids transporter. Mediates both uptake and efflux of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) with high affinity, suggesting a role in the homeostasis of thyroid hormone levels. Responsible for low affinity bidirectional transport of the aromatic amino acids, such as phenylalanine, tyrosine, tryptophan and L-3,4-dihydroxyphenylalanine (L-dopa). Plays an important role in homeostasis of aromatic amino acids.
• Tissue Specificity: Strongly expressed in kidney and skeletal muscle and at lower level in placenta and heart.
• KEGG Pathway:
  Thyroid hormone sig.ling pathway (hsa04919)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway: Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Monocarboxylate transporter 10 (SLC16A10).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[6]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[14]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Monocarboxylate transporter 10 (SLC16A10).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Monocarboxylate transporter 10 (SLC16A10).	[15]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.