Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIN6G20)

• DOT Name: Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2)
• Synonyms: EC 2.3.1.21; Carnitine palmitoyltransferase II; CPT II
• Gene Name: CPT2
• Related Disease:
  Carnitine palmitoyltransferase II deficiency
  Psoriatic arthritis
  Acute myocardial infarction
  Advanced cancer
  Arrhythmia
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiac failure
  Cardiomyopathy
  Carnitine palmitoyl transferase II deficiency, myopathic form
  Carnitine palmitoyl transferase II deficiency, neonatal form
  Carnitine palmitoyl transferase II deficiency, severe infantile form
  Colorectal carcinoma
  Congestive heart failure
  Dilated cardiomyopathy 1A
  Fatty liver disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hereditary myoglobinuria
  Hypoglycemia
  Metabolic disorder
  Metabolic myopathy
  Multiple acyl-CoA dehydrogenase deficiency
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Ovarian cancer
  Polycystic ovarian syndrome
  Type-1/2 diabetes
  Chronic renal failure
  End-stage renal disease
  Fetal growth restriction
  Glycogen storage disease V
  Influenza
  Prostate cancer
  Prostate carcinoma
  Hyperlipidemia
  Non-alcoholic fatty liver disease
  Encephalitis
  Encephalopathy, acute, infection-induced, susceptibility to, 4
  Enterovirus infection
  Hepatitis
  Hyperglycemia
  Lipid metabolism disorder
  Myopathy
• UniProt ID: CPT2_HUMAN
• EC Number: 2.3.1.21
• Pfam ID: PF00755
• Sequence:
  MVPRLLLRAWPRGPAVGPGAPSRPLSAGSGPGQYLQRSIVPTMHYQDSLPRLPIPKLEDT
  IRRYLSAQKPLLNDGQFRKTEQFCKSFENGIGKELHEQLVALDKQNKHTSYISGPWFDMY
  LSARDSVVLNFNPFMAFNPDPKSEYNDQLTRATNMTVSAIRFLKTLRAGLLEPEVFHLNP
  AKSDTITFKRLIRFVPSSLSWYGAYLVNAYPLDMSQYFRLFNSTRLPKPSRDELFTDDKA
  RHLLVLRKGNFYIFDVLDQDGNIVSPSEIQAHLKYILSDSSPAPEFPLAYLTSENRDIWA
  ELRQKLMSSGNEESLRKVDSAVFCLCLDDFPIKDLVHLSHNMLHGDGTNRWFDKSFNLII
  AKDGSTAVHFEHSWGDGVAVLRFFNEVFKDSTQTPAVTPQSQPATTDSTVTVQKLNFELT
  DALKTGITAAKEKFDATMKTLTIDCVQFQRGGKEFLKKQKLSPDAVAQLAFQMAFLRQYG
  QTVATYESCSTAAFKHGRTETIRPASVYTKRCSEAFVREPSRHSAGELQQMMVECSKYHG
  QLTKEAAMGQGFDRHLFALRHLAAAKGIILPELYLDPAYGQINHNVLSTSTLSSPAVNLG
  GFAPVVSDGFGVGYAVHDNWIGCNVSSYPGRNAREFLQCVEKALEDMFDALEGKSIKS
• Function: Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites. Reconverts acylcarnitines back into the respective acyl-CoA esters that can then undergo beta-oxidation, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters.
• KEGG Pathway:
  Fatty acid degradation (hsa00071)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  Thermogenesis (hsa04714)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Carnitine metabolism (R-HSA-200425)
  PPARA activates gene expression (R-HSA-1989781)
• BioCyc Pathway: MetaCyc:HS08187-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
Carnitine palmitoyltransferase II deficiency	DIS3GFD9	Definitive	Autosomal recessive	[1]
Psoriatic arthritis	DISLWTG2	Definitive	Biomarker	[2]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Arrhythmia	DISFF2NI	Strong	Altered Expression	[5]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[6]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[10]
Carnitine palmitoyl transferase II deficiency, myopathic form	DISM67PB	Strong	Autosomal recessive	[11]
Carnitine palmitoyl transferase II deficiency, neonatal form	DISL7VVN	Strong	Autosomal recessive	[11]
Carnitine palmitoyl transferase II deficiency, severe infantile form	DISCN42J	Strong	Autosomal recessive	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[13]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Hereditary myoglobinuria	DIS9GJQA	Strong	Biomarker	[17]
Hypoglycemia	DISRCKR7	Strong	Biomarker	[18]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[19]
Metabolic myopathy	DISSE3BW	Strong	Genetic Variation	[20]
Multiple acyl-CoA dehydrogenase deficiency	DISEFBN7	Strong	Biomarker	[21]
Myocardial infarction	DIS655KI	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[24]
Obesity	DIS47Y1K	Strong	Biomarker	[25]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[26]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[28]
Chronic renal failure	DISGG7K6	moderate	Altered Expression	[29]
End-stage renal disease	DISXA7GG	moderate	Altered Expression	[29]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[30]
Glycogen storage disease V	DISJNC0O	moderate	Biomarker	[31]
Influenza	DIS3PNU3	moderate	Genetic Variation	[32]
Prostate cancer	DISF190Y	moderate	Biomarker	[33]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[33]
Hyperlipidemia	DIS61J3S	Disputed	Biomarker	[28]
Non-alcoholic fatty liver disease	DISDG1NL	Disputed	Altered Expression	[34]
Encephalitis	DISLD1RL	Limited	Genetic Variation	[35]
Encephalopathy, acute, infection-induced, susceptibility to, 4	DISREITG	Limited	Unknown	[36]
Enterovirus infection	DISH2UDP	Limited	Genetic Variation	[35]
Hepatitis	DISXXX35	Limited	Biomarker	[37]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[38]
Lipid metabolism disorder	DISEOA7S	Limited	Biomarker	[39]
Myopathy	DISOWG27	Limited	Genetic Variation	[40]

36 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 Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[45]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[46]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[47]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[48]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[49]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[50]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[51]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[52]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[53]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[54]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[47]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[55]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[47]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[56]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[57]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[47]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[47]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[47]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[58]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[55]
Vitamin B3	DMQVRZH	Approved	Vitamin B3 decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[59]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[61]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[63]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[64]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[65]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[66]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[67]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone decreases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[68]
CITCO	DM0N634	Investigative	CITCO increases the expression of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[67]

1 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 decreases the methylation of Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2).	[60]

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] Vitamin D Ameliorates Fat Accumulation with AMPK/SIRT1 Activity in C2C12 Skeletal Muscle Cells.Nutrients. 2019 Nov 17;11(11):2806. doi: 10.3390/nu11112806.
• [3] Single nucleotide polymorphism in CPT1B and CPT2 genes and its association with blood carnitine levels in acute myocardial infarction patients.Gene. 2013 Jul 1;523(1):76-81. doi: 10.1016/j.gene.2013.03.086. Epub 2013 Apr 6.
• [4] Effects of carnitine palmitoyltransferases on cancer cellular senescence.J Cell Physiol. 2019 Feb;234(2):1707-1719. doi: 10.1002/jcp.27042. Epub 2018 Aug 2.
• [5] Vagus nerve stimulation exerts cardioprotection against myocardial ischemia/reperfusion injury predominantly through its efferent vagal fibers.Basic Res Cardiol. 2018 May 9;113(4):22. doi: 10.1007/s00395-018-0683-0.
• [6] Macrophage fatty acid oxidation inhibits atherosclerosis progression.J Mol Cell Cardiol. 2019 Feb;127:270-276. doi: 10.1016/j.yjmcc.2019.01.003. Epub 2019 Jan 9.
• [7] CPT1A/2-Mediated FAO Enhancement-A Metabolic Target in Radioresistant Breast Cancer.Front Oncol. 2019 Nov 15;9:1201. doi: 10.3389/fonc.2019.01201. eCollection 2019.
• [8] Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?.Cancer Biol Ther. 2007 Oct;6(10):1606-13. doi: 10.4161/cbt.6.10.4742. Epub 2007 Jul 13.
• [9] Targeting mitochondrial oxidative metabolism as an approach to treat heart failure.Biochim Biophys Acta. 2013 Apr;1833(4):857-65. doi: 10.1016/j.bbamcr.2012.08.014. Epub 2012 Aug 31.
• [10] Fibroblast growth factor-21 prevents diabetic cardiomyopathy via AMPK-mediated antioxidation and lipid-lowering effects in the heart.Cell Death Dis. 2018 Feb 14;9(2):227. doi: 10.1038/s41419-018-0307-5.
• [11] PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet. 2019 Nov;51(11):1560-1565. doi: 10.1038/s41588-019-0528-2.
• [12] Integrated transcriptomic analysis of distance-related field cancerization in rectal cancer patients.Oncotarget. 2017 May 15;8(37):61107-61117. doi: 10.18632/oncotarget.17864. eCollection 2017 Sep 22.
• [13] 4-O-methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK-mediated cardiac lipid metabolism improvement.J Cell Mol Med. 2019 Aug;23(8):5771-5781. doi: 10.1111/jcmm.14493. Epub 2019 Jun 14.
• [14] The adiponectin promoter activator NP-1 induces high levels of circulating TNF and weight loss in obese (fa/fa) Zucker rats.Sci Rep. 2018 Jun 29;8(1):9858. doi: 10.1038/s41598-018-27871-7.
• [15] Development of an in vitro model to study hepatitis C virus effects on hepatocellular lipotoxicity and lipid metabolism.Pathol Res Pract. 2018 Oct;214(10):1700-1706. doi: 10.1016/j.prp.2018.08.013. Epub 2018 Aug 19.
• [16] Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2.Mol Carcinog. 2019 May;58(5):749-759. doi: 10.1002/mc.22967. Epub 2019 Jan 20.
• [17] A case of CPT deficiency, homoplasmic mtDNA mutation and ragged red fibers at muscle biopsy.J Neurol Sci. 2005 Dec 15;239(1):21-4. doi: 10.1016/j.jns.2005.07.008. Epub 2005 Sep 15.
• [18] Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects.Mol Aspects Med. 2004 Oct-Dec;25(5-6):495-520. doi: 10.1016/j.mam.2004.06.004.
• [19] Abbreviated half-lives and impaired fuel utilization in carnitine palmitoyltransferase II variant fibroblasts.PLoS One. 2015 Mar 17;10(3):e0119936. doi: 10.1371/journal.pone.0119936. eCollection 2015.
• [20] Recurrent Myalgia since Early Infancy-Misleading Clinical Course in a Child with Carnitine Palmitoyltransferase-II Deficiency.Neuropediatrics. 2020 Feb;51(1):53-56. doi: 10.1055/s-0039-1694977. Epub 2019 Sep 21.
• [21] Management and diagnosis of mitochondrial fatty acid oxidation disorders: focus on very-long-chain acyl-CoA dehydrogenase deficiency.J Hum Genet. 2019 Feb;64(2):73-85. doi: 10.1038/s10038-018-0527-7. Epub 2018 Nov 6.
• [22] Qiliqiangxin Attenuates Adverse Cardiac Remodeling after Myocardial Infarction in Ovariectomized Mice via Activation of PPAR.Cell Physiol Biochem. 2017;42(3):876-888. doi: 10.1159/000478641. Epub 2017 Jun 23.
• [23] Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells. J Biol Chem. 2019 Jun 14;294(24):9342-9357.
• [24] Metabolomics reveal mitochondrial and fatty acid metabolism disorders that contribute to the development of DKD in T2DM patients.Mol Biosyst. 2017 Oct 24;13(11):2392-2400. doi: 10.1039/c7mb00167c.
• [25] Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice.Exp Cell Res. 2018 Jun 1;367(1):15-23. doi: 10.1016/j.yexcr.2018.01.027. Epub 2018 Jan 31.
• [26] Signaling pathway network alterations in human ovarian cancers identified with quantitative mitochondrial proteomics.EPMA J. 2019 Jun 8;10(2):153-172. doi: 10.1007/s13167-019-00170-5. eCollection 2019 Jun.
• [27] Differential insulin and steroidogenic signaling in insulin resistant and non-insulin resistant human luteinized granulosa cells-A study in PCOS patients.J Steroid Biochem Mol Biol. 2018 Apr;178:283-292. doi: 10.1016/j.jsbmb.2018.01.008. Epub 2018 Jan 12.
• [28] Lipid-associated metabolic signalling networks in pancreatic beta cell function.Diabetologia. 2020 Jan;63(1):10-20. doi: 10.1007/s00125-019-04976-w. Epub 2019 Aug 19.
• [29] Adiponectin receptor and adiponectin signaling in human tissue among patients with end-stage renal disease.Nephrol Dial Transplant. 2014 Dec;29(12):2268-77. doi: 10.1093/ndt/gfu249. Epub 2014 Jul 21.
• [30] Postnatal high-fat diet enhances ectopic fat deposition in pigs with intrauterine growth retardation.Eur J Nutr. 2017 Mar;56(2):483-490. doi: 10.1007/s00394-015-1093-9. Epub 2015 Dec 26.
• [31] Metabolic myopathies: the challenge of new treatments.Curr Opin Pharmacol. 2010 Jun;10(3):338-45. doi: 10.1016/j.coph.2010.02.006. Epub 2010 Mar 29.
• [32] Thermolabile CPT II variants and low blood ATP levels are closely related to severity of acute encephalopathy in Japanese children.Brain Dev. 2012 Jan;34(1):20-7. doi: 10.1016/j.braindev.2010.12.012. Epub 2011 Jan 28.
• [33] Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade.Oncotarget. 2017 Apr 21;8(34):56051-56065. doi: 10.18632/oncotarget.17359. eCollection 2017 Aug 22.
• [34] Raw Bowl Tea (Tuocha) Polyphenol Prevention of Nonalcoholic Fatty Liver Disease by Regulating Intestinal Function in Mice.Biomolecules. 2019 Sep 1;9(9):435. doi: 10.3390/biom9090435.
• [35] Association of the Polymorphism of rs1799822 on Carnitine Palmitoyltransferase II Gene with Severe Enterovirus 71 Encephalitis in Chinese Children.J Mol Neurosci. 2019 Oct;69(2):188-196. doi: 10.1007/s12031-019-01348-2. Epub 2019 Jun 14.
• [36] A variable myopathy associated with heterozygosity for the R503C mutation in the carnitine palmitoyltransferase II gene. Mol Genet Metab. 2000 Jun;70(2):134-41. doi: 10.1006/mgme.2000.3009.
• [37] L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPAR signaling.Mol Med Rep. 2016 Feb;13(2):1320-8. doi: 10.3892/mmr.2015.4639. Epub 2015 Dec 4.
• [38] Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome.Obes Rev. 2010 May;11(5):380-8. doi: 10.1111/j.1467-789X.2009.00642.x. Epub 2009 Aug 20.
• [39] Coexistence of VHL Disease and CPT2 Deficiency: A Case Report.Cancer Res Treat. 2016 Oct;48(4):1438-1442. doi: 10.4143/crt.2015.450. Epub 2016 Mar 25.
• [40] Fluxomic assay-assisted diagnosis orientation in a cohort of 11 patients with myopathic form of CPT2 deficiency.Mol Genet Metab. 2018 Apr;123(4):441-448. doi: 10.1016/j.ymgme.2018.02.005. Epub 2018 Feb 12.
• [41] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [42] 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.
• [43] 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.
• [44] 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.
• [45] 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.
• [46] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [47] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [48] 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.
• [49] 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.
• [50] 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.
• [51] 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.
• [52] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [53] 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.
• [54] Activation of the constitutive androstane receptor by monophthalates. Chem Res Toxicol. 2016 Oct 17;29(10):1651-1661.
• [55] Orlistat Displays Antitumor Activity and Enhances the Efficacy of Paclitaxel in Human Hepatoma Hep3B Cells. Chem Res Toxicol. 2019 Feb 18;32(2):255-264. doi: 10.1021/acs.chemrestox.8b00269. Epub 2019 Jan 22.
• [56] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [57] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [58] Bezafibrate upregulates carnitine palmitoyltransferase II expression and promotes mitochondrial energy crisis dissipation in fibroblasts of patients with influenza-associated encephalopathy. Mol Genet Metab. 2011 Nov;104(3):265-72. doi: 10.1016/j.ymgme.2011.07.009. Epub 2011 Jul 20.
• [59] Effects of extended-release niacin on lipid profile and adipocyte biology in patients with impaired glucose tolerance. Atherosclerosis. 2009 Jul;205(1):207-13. doi: 10.1016/j.atherosclerosis.2008.11.026. Epub 2008 Dec 3.
• [60] 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.
• [61] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [62] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [63] 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.
• [64] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [65] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [66] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [67] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.
• [68] l-Carnitine protects against 1,4-benzoquinone-induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells. Environ Toxicol. 2020 Oct;35(10):1033-1042. doi: 10.1002/tox.22939. Epub 2020 Jun 1.