Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0GHXGG)

• DOT Name: Mitochondrial pyruvate carrier 2 (MPC2)
• Synonyms: Brain protein 44
• Gene Name: MPC2
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Glioblastoma multiforme
  Glioma
  Neoplasm
  Acute myelogenous leukaemia
  Hepatocellular carcinoma
  Melanoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: MPC2_HUMAN
• Pfam ID: PF03650
• Sequence:
  MSAAGARGLRATYHRLLDKVELMLPEKLRPLYNHPAGPRTVFFWAPIMKWGLVCAGLADM
  ARPAEKLSTAQSAVLMATGFIWSRYSLVIIPKNWSLFAVNFFVGAAGASQLFRIWRYNQE
  LKAKAHK
• Function: Mediates the uptake of pyruvate into mitochondria.
• KEGG Pathway: Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway: Pyruvate metabolism (R-HSA-70268)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[2]
Melanoma	DIS1RRCY	Limited	Biomarker	[4]
Prostate cancer	DISF190Y	Limited	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Mitochondrial pyruvate carrier 2 (MPC2) affects the response to substance of Fluorouracil.	[22]
Mitoxantrone	DMM39BF	Approved	Mitochondrial pyruvate carrier 2 (MPC2) affects the response to substance of Mitoxantrone.	[22]
Cyclophosphamide	DM4O2Z7	Approved	Mitochondrial pyruvate carrier 2 (MPC2) affects the response to substance of Cyclophosphamide.	[22]

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 Mitochondrial pyruvate carrier 2 (MPC2).	[6]

16 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 Mitochondrial pyruvate carrier 2 (MPC2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[16]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Mitochondrial pyruvate carrier 2 (MPC2).	[21]

References

• [1] Prognostic role of mitochondrial pyruvate carrier in isocitrate dehydrogenase-mutant glioma.J Neurosurg. 2018 Mar 16;130(1):56-66. doi: 10.3171/2017.9.JNS172036.
• [2] Function of mitochondrial pyruvate carriers in hepatocellular carcinoma patients.Oncol Lett. 2018 Jun;15(6):9110-9116. doi: 10.3892/ol.2018.8466. Epub 2018 Apr 11.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] C-Terminal Binding Protein 1 Modulates Cellular Redox via Feedback Regulation of MPC1 and MPC2 in Melanoma Cells.Med Sci Monit. 2018 Oct 25;24:7614-7624. doi: 10.12659/MSM.912735.
• [5] MPC1 and MPC2 expressions are associated with favorable clinical outcomes in prostate cancer.BMC Cancer. 2016 Nov 16;16(1):894. doi: 10.1186/s12885-016-2941-6.
• [6] 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.
• [7] 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.
• [8] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] 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.
• [17] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] 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.