Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH07FIW)

DOT Name Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT)
Synonyms MCT; EC 2.3.1.39; Mitochondrial malonyl CoA:ACP acyltransferase; Mitochondrial malonyltransferase; malonyltransferase
Gene Name MCAT
Related Disease
B-cell lymphoma ( )
Epilepsy ( )
Hyperglycemia ( )
Matthew-Wood syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Advanced cancer ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Clear cell renal carcinoma ( )
Epithelial ovarian cancer ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Lung adenocarcinoma ( )
Metastatic malignant neoplasm ( )
Multiple endocrine neoplasia type 2A ( )
Neoplasm ( )
Obesity ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinson disease ( )
Schizophrenia ( )
Squamous cell carcinoma ( )
Triple negative breast cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Bone osteosarcoma ( )
Carcinoma ( )
Gastric cancer ( )
Lymphoma ( )
Neuroblastoma ( )
Osteosarcoma ( )
Stomach cancer ( )
T-cell lymphoma ( )
Obsolete autosomal recessive optic atrophy ( )
Adult glioblastoma ( )
Colorectal carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Non-hodgkin lymphoma ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
UniProt ID
FABD_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2C2N; 8CSP; 8CSQ; 8CSR; 8CSS
EC Number
2.3.1.39
Pfam ID
PF00698
Sequence
MSVRVARVAWVRGLGASYRRGASSFPVPPPGAQGVAELLRDATGAEEEAPWAATERRMPG
QCSVLLFPGQGSQVVGMGRGLLNYPRVRELYAAARRVLGYDLLELSLHGPQETLDRTVHC
QPAIFVASLAAVEKLHHLQPSVIENCVAAAGFSVGEFAALVFAGAMEFAEGLYAVKIRAE
AMQEASEAVPSGMLSVLGQPQSKFNFACLEAREHCKSLGIENPVCEVSNYLFPDCRVISG
HQEALRFLQKNSSKFHFRRTRMLPVSGAFHTRLMEPAVEPLTQALKAVDIKKPLVSVYSN
VHAHRYRHPGHIHKLLAQQLVSPVKWEQTMHAIYERKKGRGFPQTFEVGPGRQLGAILKS
CNMQAWKSYSAVDVLQTLEHVDLDPQEPPR
Function
Catalyzes the transfer of a malonyl moiety from malonyl-CoA to the free thiol group of the phosphopantetheine arm of the mitochondrial ACP protein (NDUFAB1). This suggests the existence of the biosynthesis of fatty acids in mitochondria.
KEGG Pathway
Fatty acid biosynthesis (hsa00061 )
Metabolic pathways (hsa01100 )
Fatty acid metabolism (hsa01212 )
Reactome Pathway
Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289 )
BioCyc Pathway
MetaCyc:HS02028-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell lymphoma DISIH1YQ Definitive Biomarker [1]
Epilepsy DISBB28L Definitive Genetic Variation [2]
Hyperglycemia DIS0BZB5 Definitive Altered Expression [3]
Matthew-Wood syndrome DISA7HR7 Definitive Altered Expression [4]
Prostate cancer DISF190Y Definitive Altered Expression [5]
Prostate carcinoma DISMJPLE Definitive Altered Expression [5]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [6]
Adenocarcinoma DIS3IHTY Strong Altered Expression [7]
Advanced cancer DISAT1Z9 Strong Biomarker [8]
Bladder cancer DISUHNM0 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Breast neoplasm DISNGJLM Strong Biomarker [11]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [12]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [13]
Glioblastoma multiforme DISK8246 Strong Biomarker [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [15]
High blood pressure DISY2OHH Strong Biomarker [16]
Lung adenocarcinoma DISD51WR Strong Biomarker [17]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [7]
Multiple endocrine neoplasia type 2A DIS7D3W2 Strong Biomarker [18]
Neoplasm DISZKGEW Strong Biomarker [19]
Obesity DIS47Y1K Strong Biomarker [20]
Ovarian cancer DISZJHAP Strong Altered Expression [13]
Ovarian neoplasm DISEAFTY Strong Altered Expression [13]
Parkinson disease DISQVHKL Strong Genetic Variation [21]
Schizophrenia DISSRV2N Strong Biomarker [22]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [23]
Triple negative breast cancer DISAMG6N Strong Biomarker [24]
Urinary bladder cancer DISDV4T7 Strong Biomarker [9]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [9]
Bone osteosarcoma DIST1004 moderate Biomarker [25]
Carcinoma DISH9F1N moderate Biomarker [26]
Gastric cancer DISXGOUK moderate Altered Expression [27]
Lymphoma DISN6V4S moderate Altered Expression [28]
Neuroblastoma DISVZBI4 moderate Biomarker [29]
Osteosarcoma DISLQ7E2 moderate Biomarker [25]
Stomach cancer DISKIJSX moderate Altered Expression [27]
T-cell lymphoma DISSXRTQ moderate Biomarker [28]
Obsolete autosomal recessive optic atrophy DISP0XVX Supportive Autosomal recessive [30]
Adult glioblastoma DISVP4LU Limited Altered Expression [31]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [32]
Lung cancer DISCM4YA Limited Genetic Variation [33]
Lung carcinoma DISTR26C Limited Genetic Variation [33]
Melanoma DIS1RRCY Limited Biomarker [34]
Non-hodgkin lymphoma DISS2Y8A Limited Altered Expression [1]
Non-insulin dependent diabetes DISK1O5Z Limited Biomarker [35]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [36]
Pancreatic cancer DISJC981 Limited Altered Expression [37]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [38]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [39]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [40]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [41]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [42]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [43]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (MCAT). [44]
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⏷ Show the Full List of 7 Drug(s)

References

1 Clinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma - MCT1 as potential target in diffuse large B cell lymphoma.Cell Oncol (Dordr). 2019 Jun;42(3):303-318. doi: 10.1007/s13402-019-00426-2. Epub 2019 Feb 21.
2 Correlation of MCT1 and ABCC2 gene polymorphisms with valproic acid resistance in patients with epilepsy on valproic acid monotherapy.Drug Metab Pharmacokinet. 2019 Jun;34(3):165-171. doi: 10.1016/j.dmpk.2018.01.006. Epub 2018 Mar 16.
3 Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus.NMR Biomed. 2018 May;31(5):e3910. doi: 10.1002/nbm.3910. Epub 2018 Mar 13.
4 miR-124 Suppresses Pancreatic Ductal Adenocarcinoma Growth by Regulating Monocarboxylate Transporter 1-Mediated Cancer Lactate Metabolism.Cell Physiol Biochem. 2018;50(3):924-935. doi: 10.1159/000494477. Epub 2018 Oct 24.
5 Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression.BMC Cancer. 2014 Mar 5;14:154. doi: 10.1186/1471-2407-14-154.
6 Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells.Oncotarget. 2017 Aug 16;8(47):82803-82823. doi: 10.18632/oncotarget.20294. eCollection 2017 Oct 10.
7 Intratumoral lactate metabolism in Barrett's esophagus and adenocarcinoma.Oncotarget. 2017 Apr 4;8(14):22894-22902. doi: 10.18632/oncotarget.15284.
8 Tumoral microvesicle-activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma.FASEB J. 2019 Apr;33(4):5690-5703. doi: 10.1096/fj.201802226R. Epub 2019 Jan 30.
9 MCT1 regulates aggressive and metabolic phenotypes in bladder cancer.J Cancer. 2018 Jun 15;9(14):2492-2501. doi: 10.7150/jca.25257. eCollection 2018.
10 Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study.Nutr Cancer. 2020;72(4):627-634. doi: 10.1080/01635581.2019.1650942. Epub 2019 Sep 9.
11 Cellular Uptake of MCT1 Inhibitors AR-C155858 and AZD3965 and Their Effects on MCT-Mediated Transport of L-Lactate in Murine 4T1 Breast Tumor Cancer Cells.AAPS J. 2019 Jan 7;21(2):13. doi: 10.1208/s12248-018-0279-5.
12 The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma.PLoS One. 2018 Feb 26;13(2):e0193477. doi: 10.1371/journal.pone.0193477. eCollection 2018.
13 Lactate dehydrogenase is correlated with clinical stage and grade and is downregulated by siSAB1 in ovarian cancer.Oncol Rep. 2018 Nov;40(5):2788-2797. doi: 10.3892/or.2018.6658. Epub 2018 Aug 17.
14 An overview of MCT1 and MCT4 in GBM: small molecule transporters with large implications.Am J Cancer Res. 2018 Oct 1;8(10):1967-1976. eCollection 2018.
15 Regulation of Acetate Utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC).Oncol Res. 2018 Jan 19;26(1):71-81. doi: 10.3727/096504017X14902648894463. Epub 2017 Mar 23.
16 Involvement of S100A4/Mts1 and associated proteins in the protective effect of fluoxetine against MCT - Induced pulmonary hypertension in rats.J Chin Med Assoc. 2018 Dec;81(12):1077-1087. doi: 10.1016/j.jcma.2018.03.013. Epub 2018 Jul 19.
17 A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma.PLoS One. 2015 Nov 5;10(11):e0142162. doi: 10.1371/journal.pone.0142162. eCollection 2015.
18 Plasma and tumor dopamine-beta-hydroxylase activity in patients with familial pheochromocytomas.Metabolism. 1978 Dec;27(12):1797-802. doi: 10.1016/0026-0495(78)90266-4.
19 Monocarboxylate transporters in cancer.Mol Metab. 2020 Mar;33:48-66. doi: 10.1016/j.molmet.2019.07.006. Epub 2019 Jul 27.
20 Monocarboxylate transporters: new players in body weight regulation.Obes Rev. 2015 Feb;16 Suppl 1:55-66. doi: 10.1111/obr.12256.
21 Dynamics of Parkinson's Disease Multimodal Complex Treatment in Germany from 2010?016: Patient Characteristics, Access to Treatment, and Formation of Regional Centers.Cells. 2019 Feb 11;8(2):151. doi: 10.3390/cells8020151.
22 The Effect of Reducing the "Jumping to Conclusions" Bias on Treatment Decision-Making Capacity in Psychosis: A Randomized Controlled Trial With Mediation Analysis.Schizophr Bull. 2019 Jun 18;45(4):784-793. doi: 10.1093/schbul/sby136.
23 STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment.Tumour Biol. 2016 Apr;37(4):5385-95. doi: 10.1007/s13277-015-4385-z. Epub 2015 Nov 12.
24 MCT-1/miR-34a/IL-6/IL-6R signaling axis promotes EMT progression, cancer stemness and M2 macrophage polarization in triple-negative breast cancer.Mol Cancer. 2019 Mar 18;18(1):42. doi: 10.1186/s12943-019-0988-0.
25 Downregulation of MCT1 inhibits tumor growth, metastasis and enhances chemotherapeutic efficacy in osteosarcoma through regulation of the NF-B pathway.Cancer Lett. 2014 Jan 1;342(1):150-8. doi: 10.1016/j.canlet.2013.08.042. Epub 2013 Sep 3.
26 Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity.Oncotarget. 2012 Nov;3(11):1401-15. doi: 10.18632/oncotarget.688.
27 MACC1 mediates chemotherapy sensitivity of 5-FU and cisplatin via regulating MCT1 expression in gastric cancer.Biochem Biophys Res Commun. 2017 Apr 8;485(3):665-671. doi: 10.1016/j.bbrc.2017.02.096. Epub 2017 Feb 21.
28 PKC inhibition of sotrastaurin has antitumor activity in diffuse large B-cell lymphoma via regulating the expression of MCT-1.Acta Biochim Biophys Sin (Shanghai). 2018 Apr 1;50(4):399-407. doi: 10.1093/abbs/gmy021.
29 The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma.Mol Pharmacol. 2006 Dec;70(6):2108-15. doi: 10.1124/mol.106.026245. Epub 2006 Sep 25.
30 Novel mutations in malonyl-CoA-acyl carrier protein transacylase provoke autosomal recessive optic neuropathy. Hum Mol Genet. 2020 Feb 1;29(3):444-458. doi: 10.1093/hmg/ddz311.
31 Lactic acid induces lactate transport and glycolysis/OXPHOS interconversion in glioblastoma.Biochem Biophys Res Commun. 2018 Sep 5;503(2):888-894. doi: 10.1016/j.bbrc.2018.06.092. Epub 2018 Jun 21.
32 MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling.Cell Death Dis. 2019 Aug 13;10(8):615. doi: 10.1038/s41419-019-1844-2.
33 Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells.Front Pharmacol. 2019 Mar 22;10:260. doi: 10.3389/fphar.2019.00260. eCollection 2019.
34 The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4.Cell Cycle. 2016 Jun 2;15(11):1462-70. doi: 10.1080/15384101.2016.1175258. Epub 2016 Apr 22.
35 Embryonic stem cell-derived pancreatic endoderm transplant with MCT1-suppressing miR-495 attenuates type II diabetes in mice.Endocr J. 2015;62(10):907-20. doi: 10.1507/endocrj.EJ15-0186. Epub 2015 Jul 25.
36 Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status.Oncotarget. 2015 Mar 30;6(9):6708-21. doi: 10.18632/oncotarget.2862.
37 Expression of Monocarboxylate Transporter 1 Is Associated With Better Prognosis and Reduced Nodal Metastasis in Pancreatic Ductal Adenocarcinoma.Pancreas. 2019 Sep;48(8):1102-1110. doi: 10.1097/MPA.0000000000001369.
38 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
39 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.
40 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.
41 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
42 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.
43 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.
44 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.