Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7OI36B)

• DOT Name: Monocarboxylate transporter 2 (SLC16A7)
• Synonyms: MCT 2; Solute carrier family 16 member 7
• Gene Name: SLC16A7
• UniProt ID: MOT2_HUMAN
• PDB ID: 7BP3
• Pfam ID: PF07690
• Sequence:
  MPPMPSAPPVHPPPDGGWGWIVVGAAFISIGFSYAFPKAVTVFFKEIQQIFHTTYSEIAW
  ISSIMLAVMYAGGPVSSVLVNKYGSRPVVIAGGLLCCLGMVLASFSSSVVQLYLTMGFIT
  GLGLAFNLQPALTIIGKYFYRKRPMANGLAMAGSPVFLSSLAPFNQYLFNTFGWKGSFLI
  LGSLLLNACVAGSLMRPLGPNQTTSKSKNKTGKTEDDSSPKKIKTKKSTWEKVNKYLDFS
  LFKHRGFLIYLSGNVIMFLGFFAPIIFLAPYAKDQGIDEYSAAFLLSVMAFVDMFARPSV
  GLIANSKYIRPRIQYFFSFAIMFNGVCHLLCPLAQDYTSLVLYAVFFGLGFGSVSSVLFE
  TLMDLVGAPRFSSAVGLVTIVECGPVLLGPPLAGKLVDLTGEYKYMYMSCGAIVVAASVW
  LLIGNAINYRLLAKERKEENARQKTRESEPLSKSKHSEDVNVKVSNAQSVTSERETNI
• Function: Proton-coupled monocarboxylate symporter. Catalyzes the rapid transport across the plasma membrane of monocarboxylates such as L-lactate, pyruvate and ketone bodies, acetoacetate, beta-hydroxybutyrate and acetate. Dimerization is functionally required and both subunits work cooperatively in transporting substrate.
• Tissue Specificity: Detected in heart and in blood lymphocytes and monocytes (at protein level) . High expression in testis, moderate to low in spleen, heart, kidney, pancreas, skeletal muscle, brain and leukocyte . Restricted expression in normal tissues, but widely expressed in cancer cells.
• Reactome Pathway: Proton-coupled monocarboxylate transport (R-HSA-433692)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Monocarboxylate transporter 2 (SLC16A7) affects the uptake of 3-iodothyronamine.	[18]

4 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 2 (SLC16A7).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Monocarboxylate transporter 2 (SLC16A7).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Monocarboxylate transporter 2 (SLC16A7).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Monocarboxylate transporter 2 (SLC16A7).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Monocarboxylate transporter 2 (SLC16A7).	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[9]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Monocarboxylate transporter 2 (SLC16A7).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Monocarboxylate transporter 2 (SLC16A7).	[11]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Monocarboxylate transporter 2 (SLC16A7).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Monocarboxylate transporter 2 (SLC16A7).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monocarboxylate transporter 2 (SLC16A7).	[16]

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] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [8] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [11] 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.
• [12] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [13] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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.
• [16] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [17] 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.
• [18] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.