Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7BIIZX)

• DOT Name: Monocarboxylate transporter 7 (SLC16A6)
• Synonyms: MCT 7; Monocarboxylate transporter 6; MCT 6; Solute carrier family 16 member 6
• Gene Name: SLC16A6
• UniProt ID: MOT7_HUMAN
• Pfam ID: PF07690
• Sequence:
  MTQNKLKLCSKANVYTEVPDGGWGWAVAVSFFFVEVFTYGIIKTFGVFFNDLMDSFNESN
  SRISWIISICVFVLTFSAPLATVLSNRFGHRLVVMLGGLLVSTGMVAASFSQEVSHMYVA
  IGIISGLGYCFSFLPTVTILSQYFGKRRSIVTAVASTGECFAVFAFAPAIMALKERIGWR
  YSLLFVGLLQLNIVIFGALLRPIFIRGPASPKIVIQENRKEAQYMLENEKTRTSIDSIDS
  GVELTTSPKNVPTHTNLELEPKADMQQVLVKTSPRPSEKKAPLLDFSILKEKSFICYALF
  GLFATLGFFAPSLYIIPLGISLGIDQDRAAFLLSTMAIAEVFGRIGAGFVLNREPIRKIY
  IELICVILLTVSLFAFTFATEFWGLMSCSIFFGFMVGTIGGTHIPLLAEDDVVGIEKMSS
  AAGVYIFIQSIAGLAGPPLAGLLVDQSKIYSRAFYSCAAGMALAAVCLALVRPCKMGLCQ
  HHHSGETKVVSHRGKTLQDIPEDFLEMDLAKNEHRVHVQMEPV
• Function: Monocarboxylate transporter selective for taurine. May associate with BSG/CD147 or EMB/GP70 ancillary proteins to mediate facilitative efflux or influx of taurine across the plasma membrane. The transport is pH- and sodium-independent. Rather low-affinity, is likely effective for taurine transport in tissues where taurine is present at high concentrations.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Monocarboxylate transporter 7 (SLC16A6) affects the response to substance of Etoposide.	[29]
Mitomycin	DMH0ZJE	Approved	Monocarboxylate transporter 7 (SLC16A6) affects the response to substance of Mitomycin.	[29]
Mitoxantrone	DMM39BF	Approved	Monocarboxylate transporter 7 (SLC16A6) affects the response to substance of Mitoxantrone.	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[11]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[12]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[13]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[14]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[15]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[16]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[17]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[17]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[19]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[27]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Monocarboxylate transporter 7 (SLC16A6).	[28]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Monocarboxylate transporter 7 (SLC16A6).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Monocarboxylate transporter 7 (SLC16A6).	[24]

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] 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] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [9] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [10] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [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] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [14] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [15] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [16] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [17] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [18] Similarities and differences between two modes of antagonism of the thyroid hormone receptor. ACS Chem Biol. 2011 Oct 21;6(10):1096-106.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] 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.
• [21] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [22] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [23] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [24] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [25] 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.
• [26] 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.
• [27] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [28] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [29] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.