Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DYFUO)

DOT Name Mitochondrial pyruvate carrier 1 (MPC1)
Synonyms Brain protein 44-like protein
Gene Name MPC1
Related Disease
Mitochondrial disease ( )
Adenoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Biliary tract cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Cholangiocarcinoma ( )
Cowden disease ( )
Drug dependence ( )
Glioblastoma multiforme ( )
Glioma ( )
Intrahepatic cholangiocarcinoma ( )
Lung adenocarcinoma ( )
Mitochondrial pyruvate carrier deficiency ( )
Prostate cancer ( )
Prostate carcinoma ( )
Substance abuse ( )
Substance dependence ( )
Dermatomyositis ( )
Type-1/2 diabetes ( )
Plasma cell myeloma ( )
Clear cell renal carcinoma ( )
Gastric cancer ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Myotonic dystrophy type 1 ( )
Neoplasm ( )
Patent ductus arteriosus ( )
Renal cell carcinoma ( )
Stomach cancer ( )
UniProt ID
MPC1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF03650
Sequence
MAGALVRKAADYVRSKDFRDYLMSTHFWGPVANWGLPIAAINDMKKSPEIISGRMTFALC
CYSLTFMRFAYKVQPRNWLLFACHATNEVAQLIQGGRLIKHEMTKTASA
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

31 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Mitochondrial disease DISKAHA3 Definitive Autosomal recessive [1]
Adenoma DIS78ZEV Strong Biomarker [2]
Adult glioblastoma DISVP4LU Strong Genetic Variation [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Biliary tract cancer DISBNYQL Strong Altered Expression [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Cholangiocarcinoma DIS71F6X Strong Altered Expression [7]
Cowden disease DISMYKCE Strong Genetic Variation [8]
Drug dependence DIS9IXRC Strong Biomarker [9]
Glioblastoma multiforme DISK8246 Strong Biomarker [3]
Glioma DIS5RPEH Strong Biomarker [10]
Intrahepatic cholangiocarcinoma DIS6GOC8 Strong Biomarker [5]
Lung adenocarcinoma DISD51WR Strong Biomarker [11]
Mitochondrial pyruvate carrier deficiency DISTTZKG Strong Autosomal recessive [12]
Prostate cancer DISF190Y Strong Biomarker [5]
Prostate carcinoma DISMJPLE Strong Biomarker [5]
Substance abuse DIS327VW Strong Biomarker [9]
Substance dependence DISDRAAR Strong Biomarker [9]
Dermatomyositis DIS50C5O moderate Altered Expression [13]
Type-1/2 diabetes DISIUHAP moderate Altered Expression [13]
Plasma cell myeloma DIS0DFZ0 Disputed Biomarker [14]
Clear cell renal carcinoma DISBXRFJ Limited Biomarker [15]
Gastric cancer DISXGOUK Limited Biomarker [16]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [17]
Lung cancer DISCM4YA Limited Altered Expression [18]
Myotonic dystrophy type 1 DISJC0OX Limited Altered Expression [13]
Neoplasm DISZKGEW Limited Altered Expression [19]
Patent ductus arteriosus DIS9P8YS Limited Altered Expression [19]
Renal cell carcinoma DISQZ2X8 Limited Biomarker [15]
Stomach cancer DISKIJSX Limited Biomarker [16]
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⏷ Show the Full List of 31 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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 increases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [20]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [21]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [22]
Acetaminophen DMUIE76 Approved Acetaminophen affects the expression of Mitochondrial pyruvate carrier 1 (MPC1). [23]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [24]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [26]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Mitochondrial pyruvate carrier 1 (MPC1). [27]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [28]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [29]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [30]
Propofol DMB4OLE Approved Propofol decreases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [31]
Sevoflurane DMC9O43 Approved Sevoflurane increases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [31]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [32]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Mitochondrial pyruvate carrier 1 (MPC1). [33]
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⏷ Show the Full List of 14 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Mitochondrial pyruvate carrier 1 (MPC1). [25]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier.Cell Metab. 2020 Feb 4;31(2):284-300.e7. doi: 10.1016/j.cmet.2019.11.002. Epub 2019 Dec 5.
3 MPC1 deletion is associated with poor prognosis and temozolomide resistance in glioblastoma.J Neurooncol. 2019 Sep;144(2):293-301. doi: 10.1007/s11060-019-03226-8. Epub 2019 Jun 24.
4 Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance.Cancer Sci. 2019 Apr;110(4):1331-1339. doi: 10.1111/cas.13980.
5 Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma.Oncol Rep. 2018 Mar;39(3):1276-1282. doi: 10.3892/or.2017.6172. Epub 2017 Dec 20.
6 Quantitative proteomics study of breast cancer cell lines isolated from a single patient: discovery of TIMM17A as a marker for breast cancer.Proteomics. 2010 Apr;10(7):1374-90. doi: 10.1002/pmic.200900380.
7 PGC1 promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect.Cell Death Dis. 2018 May 1;9(5):466. doi: 10.1038/s41419-018-0494-0.
8 AGP30: Cd tolerance related gene associate with mitochondrial pyruvate carrier 1.Plant Signal Behav. 2019;14(9):1629269. doi: 10.1080/15592324.2019.1629269. Epub 2019 Jun 14.
9 Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
10 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.
11 MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway.Cell Death Dis. 2019 Feb 15;10(3):148. doi: 10.1038/s41419-019-1324-8.
12 A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012 Jul 6;337(6090):96-100. doi: 10.1126/science.1218099. Epub 2012 May 24.
13 Detection of serum MCP-1 and TGF-1 in polymyositis/dermatomyositis patients and its significance.Eur J Med Res. 2019 Feb 14;24(1):12. doi: 10.1186/s40001-019-0368-7.
14 Clinical effects of CD33 and MPC-1 on the prognosis of multiple myeloma treated with bortezomib.Leuk Lymphoma. 2019 Sep;60(9):2152-2157. doi: 10.1080/10428194.2019.1574003. Epub 2019 Mar 19.
15 Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the prognosis of human renal cell carcinoma.Lab Invest. 2019 Feb;99(2):191-199. doi: 10.1038/s41374-018-0138-0. Epub 2018 Oct 5.
16 Overexpression of MPC1 inhibits the proliferation, migration, invasion, and stem cell-like properties of gastric cancer cells.Onco Targets Ther. 2017 Oct 24;10:5151-5163. doi: 10.2147/OTT.S148681. eCollection 2017.
17 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.
18 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.
19 A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism.Oncogene. 2020 Jan;39(5):1140-1151. doi: 10.1038/s41388-019-1051-8. Epub 2019 Oct 22.
20 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
21 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
22 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.
23 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.
24 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
25 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
26 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.
27 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.
28 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
29 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.
30 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
31 Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms. Cell Biol Toxicol. 2023 Aug;39(4):1395-1411. doi: 10.1007/s10565-022-09766-6. Epub 2022 Oct 8.
32 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
33 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.