Details of Drug Off-Target (DOT)

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

• DOT Name: Calpastatin (CAST)
• Synonyms: Calpain inhibitor; Sperm BS-17 component
• Gene Name: CAST
• Related Disease:
  Multiple sclerosis
  Stroke
  Acute liver failure
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Ankylosing spondylitis
  Arteriosclerosis
  Atherosclerosis
  Autism
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Colitis
  Congestive heart failure
  Cystic fibrosis
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Huntington disease
  Inflammatory bowel disease
  Keratoconus
  Lung adenocarcinoma
  Melanoma
  Myelodysplastic syndrome
  Neoplasm
  Obesity
  Osteoarthritis
  Pancreatic cancer
  Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome
  Pulmonary fibrosis
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Systemic sclerosis
  Amyotrophic lateral sclerosis
  Gastric cancer
  High blood pressure
  Small-cell lung cancer
  Stomach cancer
  Colonic neoplasm
  Colorectal carcinoma
  Myocardial infarction
  Nasopharyngeal carcinoma
  Nervous system disease
  Neuroblastoma
  Ovarian cancer
  Parkinson disease
  Psoriasis
  Spinocerebellar ataxia type 3
  Type-1/2 diabetes
• UniProt ID: ICAL_HUMAN
• Pfam ID: PF00748
• Sequence:
  MNPTETKAIPVSQQMEGPHLPNKKKHKKQAVKTEPEKKSQSTKLSVVHEKKSQEGKPKEH
  TEPKSLPKQASDTGSNDAHNKKAVSRSAEQQPSEKSTEPKTKPQDMISAGGESVAGITAI
  SGKPGDKKKEKKSLTPAVPVESKPDKPSGKSGMDAALDDLIDTLGGPEETEEENTTYTGP
  EVSDPMSSTYIEELGKREVTIPPKYRELLAKKEGITGPPADSSKPIGPDDAIDALSSDFT
  CGSPTAAGKKTEKEESTEVLKAQSAGTVRSAAPPQEKKRKVEKDTMSDQALEALSASLGT
  RQAEPELDLRSIKEVDEAKAKEEKLEKCGEDDETIPSEYRLKPATDKDGKPLLPEPEEKP
  KPRSESELIDELSEDFDRSECKEKPSKPTEKTEESKAAAPAPVSEAVCRTSMCSIQSAPP
  EPATLKGTVPDDAVEALADSLGKKEADPEDGKPVMDKVKEKAKEEDREKLGEKEETIPPD
  YRLEEVKDKDGKPLLPKESKEQLPPMSEDFLLDALSEDFSGPQNASSLKFEDAKLAAAIS
  EVVSQTPASTTQAGAPPRDTSQSDKDLDDALDKLSDSLGQRQPDPDENKPMEDKVKEKAK
  AEHRDKLGERDDTIPPEYRHLLDDNGQDKPVKPPTKKSEDSKKPADDQDPIDALSGDLDS
  CPSTTETSQNTAKDKCKKAASSSKAPKNGGKAKDSAKTTEETSKPKDD
• Function: Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.
• KEGG Pathway: Shigellosis (hsa05131)
• Reactome Pathway:
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[1]
Stroke	DISX6UHX	Definitive	Biomarker	[2]
Acute liver failure	DIS5EZKX	Strong	Therapeutic	[3]
Adult glioblastoma	DISVP4LU	Strong	Posttranslational Modification	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[6]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[7]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[7]
Autism	DISV4V1Z	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Cardiac failure	DISDC067	Strong	Genetic Variation	[10]
Colitis	DISAF7DD	Strong	Biomarker	[11]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[10]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Huntington disease	DISQPLA4	Strong	Biomarker	[14]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[11]
Keratoconus	DISOONXH	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[16]
Melanoma	DIS1RRCY	Strong	Altered Expression	[17]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Pancreatic cancer	DISJC981	Strong	Biomarker	[22]
Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome	DIS07A0Y	Strong	Autosomal recessive	[23]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[27]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[28]
Gastric cancer	DISXGOUK	moderate	Biomarker	[29]
High blood pressure	DISY2OHH	moderate	Biomarker	[30]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[31]
Stomach cancer	DISKIJSX	moderate	Biomarker	[29]
Colonic neoplasm	DISSZ04P	Limited	Altered Expression	[32]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[32]
Myocardial infarction	DIS655KI	Limited	Biomarker	[33]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[34]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[35]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[36]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[37]
Parkinson disease	DISQVHKL	Limited	Biomarker	[35]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[38]
Spinocerebellar ataxia type 3	DISQBQID	Limited	Biomarker	[39]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[40]

18 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 Calpastatin (CAST).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calpastatin (CAST).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Calpastatin (CAST).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calpastatin (CAST).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calpastatin (CAST).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calpastatin (CAST).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calpastatin (CAST).	[47]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calpastatin (CAST).	[48]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Calpastatin (CAST).	[49]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Calpastatin (CAST).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Calpastatin (CAST).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Calpastatin (CAST).	[53]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calpastatin (CAST).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Calpastatin (CAST).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Calpastatin (CAST).	[58]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calpastatin (CAST).	[59]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Calpastatin (CAST).	[60]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Calpastatin (CAST).	[61]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Calpastatin (CAST).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Calpastatin (CAST).	[55]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Calpastatin (CAST).	[56]

References

• [1] Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients.J Neuroimmunol. 2011 Mar;232(1-2):179-85. doi: 10.1016/j.jneuroim.2010.09.030. Epub 2010 Nov 13.
• [2] Neuroprotective actions of aminoguanidine involve reduced the activation of calpain and caspase-3 in a rat model of stroke.Neurochem Int. 2010 Mar;56(4):634-41. doi: 10.1016/j.neuint.2010.01.009. Epub 2010 Jan 29.
• [3] Upregulation of calpastatin in regenerating and developing rat liver: role in resistance against hepatotoxicity.Hepatology. 2006 Aug;44(2):379-88. doi: 10.1002/hep.21250.
• [4] Calpastatin phosphorylation regulates radiation-induced calpain activity in glioblastoma.Oncotarget. 2018 Feb 19;9(18):14597-14607. doi: 10.18632/oncotarget.24523. eCollection 2018 Mar 6.
• [5] Calpastatin Mediates Development of Alzheimer's Disease in Diabetes.J Alzheimers Dis. 2019;68(3):1051-1059. doi: 10.3233/JAD-190004.
• [6] Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci.Nat Genet. 2010 Feb;42(2):123-7. doi: 10.1038/ng.513. Epub 2010 Jan 10.
• [7] Calpain inhibitor I attenuates atherosclerosis and inflammation in atherosclerotic rats through eNOS/NO/NF-B pathway.Can J Physiol Pharmacol. 2018 Jan;96(1):60-67. doi: 10.1139/cjpp-2016-0652. Epub 2017 Jul 30.
• [8] Head circumference and child ADHD symptoms and cognitive functioning: results from a large population-based cohort study.Eur Child Adolesc Psychiatry. 2019 Mar;28(3):377-388. doi: 10.1007/s00787-018-1202-4. Epub 2018 Jul 19.
• [9] Anti-breast cancer effects of histone deacetylase inhibitors and calpain inhibitor.Anticancer Res. 2012 Jul;32(7):2523-9.
• [10] A novel paradigm for therapeutic basis of advanced heart failure--assessment by gene therapy.Pharmacol Ther. 2005 Jul;107(1):31-43. doi: 10.1016/j.pharmthera.2004.12.006. Epub 2005 Apr 13.
• [11] Calpastatin prevents NF-B-mediated hyperactivation of macrophages and attenuates colitis.J Immunol. 2013 Oct 1;191(7):3778-88. doi: 10.4049/jimmunol.1300972. Epub 2013 Aug 28.
• [12] Calpain inhibition promotes the rescue of F(508)del-CFTR in PBMC from cystic fibrosis patients.PLoS One. 2013 Jun 13;8(6):e66089. doi: 10.1371/journal.pone.0066089. Print 2013.
• [13] Ibulocydine sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis via calpain-mediated Bax cleavage.Int J Biochem Cell Biol. 2017 Feb;83:47-55. doi: 10.1016/j.biocel.2016.12.001. Epub 2016 Dec 5.
• [14] Calpastatin ablation aggravates the molecular phenotype in cell and animal models of Huntington disease.Neuropharmacology. 2018 May 1;133:94-106. doi: 10.1016/j.neuropharm.2018.01.022.
• [15] Evaluating the association between calpastatin (CAST) gene and keratoconus in the Han Chinese population.Gene. 2018 May 5;653:10-13. doi: 10.1016/j.gene.2018.02.016. Epub 2018 Feb 8.
• [16] The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR.J Thorac Dis. 2017 Aug;9(8):2397-2403. doi: 10.21037/jtd.2017.07.02.
• [17] Preventing Calpain Externalization by Reducing ABCA1 Activity with Probenecid Limits Melanoma Angiogenesis and Development.J Invest Dermatol. 2020 Feb;140(2):445-454. doi: 10.1016/j.jid.2019.06.148. Epub 2019 Aug 16.
• [18] A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes.Nat Med. 2016 Jul;22(7):727-34. doi: 10.1038/nm.4127. Epub 2016 Jun 13.
• [19] Blocking the Cleavage of Filamin A by Calpain Inhibitor Decreases Tumor Cell Growth.Anticancer Res. 2018 Apr;38(4):2079-2085. doi: 10.21873/anticanres.12447.
• [20] Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice.Sci Rep. 2017 Oct 31;7(1):14398. doi: 10.1038/s41598-017-14719-9.
• [21] Inflammatory cytokines induced down-regulation of m-calpain mRNA expression in fibroblastic synoviocytes from patients with osteoarthritis and rheumatoid arthritis.Biochem Biophys Res Commun. 1999 Dec 20;266(2):341-6. doi: 10.1006/bbrc.1999.1819.
• [22] Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer-stromal interactions in a mouse xenograft model.Cancer Sci. 2016 Oct;107(10):1443-1452. doi: 10.1111/cas.13024. Epub 2016 Sep 24.
• [23] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [24] The calpain inhibitor calpeptin prevents bleomycin-induced pulmonary fibrosis in mice.Clin Exp Immunol. 2010 Dec;162(3):560-7. doi: 10.1111/j.1365-2249.2010.04257.x. Epub 2010 Sep 15.
• [25] Overexpression of a minimal domain of calpastatin suppresses IL-6 production and Th17 development via reduced NF-B and increased STAT5 signals.PLoS One. 2011;6(10):e27020. doi: 10.1371/journal.pone.0027020. Epub 2011 Oct 27.
• [26] Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus.J Autoimmun. 2002 Aug-Sep;19(1-2):55-61. doi: 10.1006/jaut.2002.0598.
• [27] Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic rheumatic diseases.Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7267-71. doi: 10.1073/pnas.92.16.7267.
• [28] Calpastatin inhibits motor neuron death and increases survival of hSOD1(G93A) mice.J Neurochem. 2016 Apr;137(2):253-65. doi: 10.1111/jnc.13536. Epub 2016 Mar 23.
• [29] Comparison of the protein expression of calpain-1, calpain-2, calpastatin and calmodulin between gastric cancer and normal gastric mucosa.Oncol Lett. 2017 Sep;14(3):3705-3710. doi: 10.3892/ol.2017.6617. Epub 2017 Jul 20.
• [30] Extracellular Calpain/Calpastatin Balance Is Involved in the Progression of Pulmonary Hypertension.Am J Respir Cell Mol Biol. 2016 Sep;55(3):337-51. doi: 10.1165/rcmb.2015-0257OC.
• [31] Gene/protein expression of CAPN1/2-CAST system members is associated with ERK1/2 kinases activity as well as progression and clinical outcome in human laryngeal cancer.Tumour Biol. 2016 Oct;37(10):13185-13203. doi: 10.1007/s13277-016-5178-8. Epub 2016 Jul 25.
• [32] Overexpression of m-calpain in human colorectal adenocarcinomas.Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1604-9.
• [33] Over-expression of calpastatin attenuates myocardial injury following myocardial infarction by inhibiting endoplasmic reticulum stress.J Thorac Dis. 2018 Sep;10(9):5283-5297. doi: 10.21037/jtd.2018.08.133.
• [34] Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca(2+)/calpain/ITG4 axis.Biol Open. 2017 Jun 15;6(6):914-922. doi: 10.1242/bio.024646.
• [35] SNPs in CAST are associated with Parkinson disease: a confirmation study.Am J Med Genet B Neuropsychiatr Genet. 2010 Jun 5;153B(4):973-9. doi: 10.1002/ajmg.b.31061.
• [36] Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines.Int J Oncol. 2019 Dec;55(6):1372-1384. doi: 10.3892/ijo.2019.4896. Epub 2019 Oct 7.
• [37] Calpain-2 expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer.J Cell Mol Med. 2012 Oct;16(10):2422-8. doi: 10.1111/j.1582-4934.2012.01559.x.
• [38] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [39] Calpain inhibition reduces ataxin-3 cleavage alleviating neuropathology and motor impairments in mouse models of Machado-Joseph disease.Hum Mol Genet. 2014 Sep 15;23(18):4932-44. doi: 10.1093/hmg/ddu209. Epub 2014 May 9.
• [40] Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes.Circ Res. 2015 Jul 3;117(2):157-65. doi: 10.1161/CIRCRESAHA.117.305784. Epub 2015 May 5.
• [41] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [42] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [45] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [46] 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.
• [47] 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.
• [48] 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.
• [49] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [50] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [51] Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
• [52] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [53] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [54] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [55] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [56] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [57] 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.
• [58] 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.
• [59] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [60] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [61] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.