Details of Drug Off-Target (DOT)

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

• DOT Name: Monocarboxylate transporter 9 (SLC16A9)
• Synonyms: MCT 9; Solute carrier family 16 member 9
• Gene Name: SLC16A9
• UniProt ID: MOT9_HUMAN
• Pfam ID: PF07690
• Sequence:
  MELKKSPDGGWGWVIVFVSFLTQFLCYGSPLAVGVLYIEWLDAFGEGKGKTAWVGSLASG
  VGLLASPVCSLCVSSFGARPVTIFSGFMVAGGLMLSSFAPNIYFLFFSYGIVVGLGCGLL
  YTATVTITCQYFDDRRGLALGLISTGSSVGLFIYAALQRMLVEFYGLDGCLLIVGALALN
  ILACGSLMRPLQSSDCPLPKKIAPEDLPDKYSIYNEKGKNLEENINILDKSYSSEEKCRI
  TLANGDWKQDSLLHKNPTVTHTKEPETYKKKVAEQTYFCKQLAKRKWQLYKNYCGETVAL
  FKNKVFSALFIAILLFDIGGFPPSLLMEDVARSSNVKEEEFIMPLISIIGIMTAVGKLLL
  GILADFKWINTLYLYVATLIIMGLALCAIPFAKSYVTLALLSGILGFLTGNWSIFPYVTT
  KTVGIEKLAHAYGILMFFAGLGNSLGPPIVGWFYDWTQTYDIAFYFSGFCVLLGGFILLL
  AALPSWDTCNKQLPKPAPTTFLYKVASNV
• Function: Extracellular pH-and Na(+)-sensitive low-affinity creatine transporter. Functions also as a pH-independent carnitine efflux transporter.

Molecular Interaction Atlas (MIA) of This DOT

14 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 9 (SLC16A9).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Monocarboxylate transporter 9 (SLC16A9).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Monocarboxylate transporter 9 (SLC16A9).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Monocarboxylate transporter 9 (SLC16A9).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Monocarboxylate transporter 9 (SLC16A9).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Monocarboxylate transporter 9 (SLC16A9).	[6]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Monocarboxylate transporter 9 (SLC16A9).	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Monocarboxylate transporter 9 (SLC16A9).	[8]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Monocarboxylate transporter 9 (SLC16A9).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Monocarboxylate transporter 9 (SLC16A9).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Monocarboxylate transporter 9 (SLC16A9).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Monocarboxylate transporter 9 (SLC16A9).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Monocarboxylate transporter 9 (SLC16A9).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Monocarboxylate transporter 9 (SLC16A9).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Monocarboxylate transporter 9 (SLC16A9).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Monocarboxylate transporter 9 (SLC16A9).	[14]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [8] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [9] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.