Details of Drug Off-Target (DOT)

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

• DOT Name: Rho guanine nucleotide exchange factor 2 (ARHGEF2)
• Synonyms: Guanine nucleotide exchange factor H1; GEF-H1; Microtubule-regulated Rho-GEF; Proliferating cell nucleolar antigen p40
• Gene Name: ARHGEF2
• Related Disease:
  Multiple sclerosis
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Carcinoma
  Familial adenomatous polyposis
  Glioblastoma multiforme
  Glioma
  HIV infectious disease
  Inflammatory bowel disease
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Nervous system inflammation
  Neurodevelopmental disorder
  Osteoarthritis
  Prostate cancer
  Psoriasis
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
  Tuberculosis
  Ulcerative colitis
  Aarskog-Scott syndrome, X-linked
  Hepatocellular carcinoma
  Mycobacterium infection
  Neuroblastoma
  Pancreatic cancer
  Prostate carcinoma
  Type-1/2 diabetes
  Melanoma
  Acute myelogenous leukaemia
  Atopic dermatitis
  Colitis
  Colon cancer
  Colon carcinoma
  Gastric cancer
  Leukodystrophy
  Neoplasm
  Neurodevelopmental disorder with midbrain and hindbrain malformations
  Non-small-cell lung cancer
  Stomach cancer
  Type-1 diabetes
• UniProt ID: ARHG2_HUMAN
• PDB ID: 5EFX ; 7G80 ; 7G81 ; 7G82 ; 7G83 ; 7G84 ; 7G85 ; 7G86 ; 7G87 ; 7G88 ; 7G89 ; 7G8A ; 7G8B ; 7G8C ; 7G8D ; 7G8E ; 7G8F ; 7G8G ; 7G8H ; 7G8I ; 7G8J ; 7G8K ; 7G8L ; 7G8M ; 7G8N ; 7G8O ; 7G8P ; 7G8Q ; 7G8R ; 7G8S ; 7G8T ; 7G8U ; 7G8V ; 7G8W ; 7G8X ; 7G8Y ; 7G8Z ; 7G90 ; 7G91 ; 7G92 ; 7G93 ; 7G94 ; 7G95 ; 7G96 ; 7G97 ; 7G98 ; 7G99 ; 7G9A ; 7G9B ; 7G9C ; 7G9D ; 7G9E ; 7G9F ; 7G9G ; 7G9H ; 7G9I ; 7G9J ; 8BNT
• Pfam ID: PF17838 ; PF00621
• Sequence:
  MSRIESLTRARIDRSRELASKTREKEKMKEAKDARYTNGHLFTTISVSGMTMCYACNKSI
  TAKEALICPTCNVTIHNRCKDTLANCTKVKQKQQKAALLKNNTALQSVSLRSKTTIRERP
  SSAIYPSDSFRQSLLGSRRGRSSLSLAKSVSTTNIAGHFNDESPLGLRRILSQSTDSLNM
  RNRTLSVESLIDEAEVIYSELMSDFEMDEKDFAADSWSLAVDSSFLQQHKKEVMKQQDVI
  YELIQTELHHVRTLKIMTRLFRTGMLEELHLEPGVVQGLFPCVDELSDIHTRFLSQLLER
  RRQALCPGSTRNFVIHRLGDLLISQFSGPSAEQMCKTYSEFCSRHSKALKLYKELYARDK
  RFQQFIRKVTRPAVLKRHGVQECILLVTQRITKYPLLISRILQHSHGIEEERQDLTTALG
  LVKELLSNVDEGIYQLEKGARLQEIYNRMDPRAQTPVPGKGPFGREELLRRKLIHDGCLL
  WKTATGRFKDVLVLLMTDVLVFLQEKDQKYIFPTLDKPSVVSLQNLIVRDIANQEKGMFL
  ISAAPPEMYEVHTASRDDRSTWIRVIQQSVRTCPSREDFPLIETEDEAYLRRIKMELQQK
  DRALVELLREKVGLFAEMTHFQAEEDGGSGMALPTLPRGLFRSESLESPRGERLLQDAIR
  EVEGLKDLLVGPGVELLLTPREPALPLEPDSGGNTSPGVTANGEARTFNGSIELCRADSD
  SSQRDRNGNQLRSPQEEALQRLVNLYGLLHGLQAAVAQQDTLMEARFPEGPERREKLCRA
  NSRDGEAGRAGAAPVAPEKQATELALLQRQHALLQEELRRCRRLGEERATEAGSLEARLR
  ESEQARALLEREAEEARRQLAALGQTEPLPAEAPWARRPVDPRRRSLPAGDALYLSFNPP
  QPSRGTDRLDLPVTTRSVHRNFEDRERQELGSPEERLQDSSDPDTGSEEEGSSRLSPPHS
  PRDFTRMQDIPEETESRDGEAVASES
• Function: Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability. Involved in neuronal progenitor cell division and differentiation. Involved in the migration of precerebellar neurons.
• KEGG Pathway:
  Tight junction (hsa04530)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  G alpha (12/13) signalling events (R-HSA-416482)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  NRAGE signals death through JNK (R-HSA-193648)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[10]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[15]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[16]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[18]
Psoriasis	DIS59VMN	Strong	Biomarker	[19]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[20]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[6]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[21]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[22]
Aarskog-Scott syndrome, X-linked	DISNHV62	moderate	Genetic Variation	[23]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[24]
Mycobacterium infection	DISNSMUD	moderate	Genetic Variation	[25]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[26]
Pancreatic cancer	DISJC981	moderate	Biomarker	[27]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[18]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[28]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[29]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[30]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[31]
Colitis	DISAF7DD	Limited	Altered Expression	[32]
Colon cancer	DISVC52G	Limited	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[33]
Leukodystrophy	DISVY1TT	Limited	Genetic Variation	[34]
Neoplasm	DISZKGEW	Limited	Biomarker	[35]
Neurodevelopmental disorder with midbrain and hindbrain malformations	DISWGLAN	Limited	Autosomal recessive	[12]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[36]
Stomach cancer	DISKIJSX	Limited	Biomarker	[33]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[37]

23 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 Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[43]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[47]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[48]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[45]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[49]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[50]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[51]
Mebendazole	DMO14SG	Approved	Mebendazole decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[52]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[54]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[56]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[59]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[60]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[61]

3 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 Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[57]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Rho guanine nucleotide exchange factor 2 (ARHGEF2).	[57]

References

• [1] LRCH1 interferes with DOCK8-Cdc42-induced T cell migration and ameliorates experimental autoimmune encephalomyelitis.J Exp Med. 2017 Jan;214(1):209-226. doi: 10.1084/jem.20160068.
• [2] SGEF Is Regulated via TWEAK/Fn14/NF-B Signaling and Promotes Survival by Modulation of the DNA Repair Response to Temozolomide.Mol Cancer Res. 2016 Mar;14(3):302-12. doi: 10.1158/1541-7786.MCR-15-0183. Epub 2016 Jan 13.
• [3] Increased expression of GEF-H1 promotes colon cancer progression by RhoA signaling.Pathol Res Pract. 2019 May;215(5):1012-1019. doi: 10.1016/j.prp.2019.02.008. Epub 2019 Feb 27.
• [4] The left frontal cortex supports reserve in aging by enhancing functional network efficiency.Alzheimers Res Ther. 2018 Mar 6;10(1):28. doi: 10.1186/s13195-018-0358-y.
• [5] Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.Neurobiol Aging. 2013 Jan;34(1):357.e7-19. doi: 10.1016/j.neurobiolaging.2012.07.017. Epub 2012 Sep 5.
• [6] High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus.Arthritis Rheumatol. 2020 Jan;72(1):89-99. doi: 10.1002/art.41054.
• [7] P-Rex1 is dispensable for Erk activation and mitogenesis in breast cancer.Oncotarget. 2018 Jun 19;9(47):28612-28624. doi: 10.18632/oncotarget.25584. eCollection 2018 Jun 19.
• [8] RETRACTED ARTICLE: Cervical adenosquamous carcinoma: detailed analysis of morphology, immunohistochemical profile, and clinical outcomes in 59 cases.Mod Pathol. 2019 Feb;32(2):269-279. doi: 10.1038/s41379-018-0123-6. Epub 2018 Sep 26.
• [9] Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism.J Biol Chem. 2007 Feb 16;282(7):4238-4242. doi: 10.1074/jbc.C600234200. Epub 2006 Dec 26.
• [10] Disruption of MAP kinase activation and nuclear factor binding to the IL-12 p40 promoter in HIV-infected myeloid cells.Clin Exp Immunol. 2004 Aug;137(2):329-40. doi: 10.1111/j.1365-2249.2004.02513.x.
• [11] Allergic and Immunologic Perspectives of Inflammatory Bowel Disease.Clin Rev Allergy Immunol. 2019 Oct;57(2):179-193. doi: 10.1007/s12016-018-8690-3.
• [12] Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation. PLoS Genet. 2017 Apr 28;13(4):e1006746. doi: 10.1371/journal.pgen.1006746. eCollection 2017 Apr.
• [13] Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer.Sci Rep. 2019 Feb 4;9(1):1319. doi: 10.1038/s41598-018-37722-0.
• [14] Biomarkers in the diagnosis of pleural diseases: a 2018 update.Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808660. doi: 10.1177/1753466618808660.
• [15] Silencing c-Rel in macrophages dampens Th1 and Th17 immune responses and alleviates experimental autoimmune encephalomyelitis in mice.Immunol Cell Biol. 2017 Aug;95(7):593-600. doi: 10.1038/icb.2017.11. Epub 2017 Feb 16.
• [16] Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons.J Genet Genomics. 2019 Feb;46(2):87-96. doi: 10.1016/j.jgg.2019.02.003. Epub 2019 Feb 23.
• [17] IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.Arthritis Res Ther. 2018 Jun 7;20(1):115. doi: 10.1186/s13075-018-1582-3.
• [18] Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-.Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11482-11487. doi: 10.1073/pnas.1705536114. Epub 2017 Oct 9.
• [19] Anti-IL-12/IL-23p40 antibody ameliorates dermatitis and skin barrier dysfunction in mice with imiquimod-induced psoriasis-like dermatitis.Eur J Pharmacol. 2018 Jun 5;828:26-30. doi: 10.1016/j.ejphar.2018.03.018. Epub 2018 Mar 12.
• [20] Wnt5a induces ROR1 to associate with 14-3-3 for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.Leukemia. 2017 Dec;31(12):2608-2614. doi: 10.1038/leu.2017.132. Epub 2017 May 3.
• [21] Guanine nucleotide exchange factor -H1 promotes inflammatory cytokine production and intracellular mycobacterial elimination in macrophages.Cell Cycle. 2017 Sep 17;16(18):1695-1704. doi: 10.1080/15384101.2017.1347739. Epub 2017 Aug 7.
• [22] Expert opinion on interleukin-12/23 and interleukin-23 antagonists as potential therapeutic options for the treatment of inflammatory bowel disease.Expert Opin Investig Drugs. 2019 May;28(5):473-479. doi: 10.1080/13543784.2019.1597053. Epub 2019 Mar 26.
• [23] Proline-rich domain plays a crucial role in extracellular stimuli-responsive translocation of a Cdc42 guanine nucleotide exchange factor, FGD1.Biol Pharm Bull. 2010;33(1):35-9. doi: 10.1248/bpb.33.35.
• [24] Long-Read RNA Sequencing Identifies Alternative Splice Variants in Hepatocellular Carcinoma and Tumor-Specific Isoforms.Hepatology. 2019 Sep;70(3):1011-1025. doi: 10.1002/hep.30500. Epub 2019 Mar 22.
• [25] Chronic Disseminated Salmonellosis in a Patient With Interleukin-12p40 Deficiency.Pediatr Infect Dis J. 2018 Jan;37(1):90-93. doi: 10.1097/INF.0000000000001701.
• [26] Involvement of p114-RhoGEF and Lfc in Wnt-3a- and dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells.Mol Biol Cell. 2010 Oct 15;21(20):3590-600. doi: 10.1091/mbc.E10-02-0095. Epub 2010 Sep 1.
• [27] An oncogenic KRAS transcription program activates the RHOGEF ARHGEF2 to mediate transformed phenotypes in pancreatic cancer.Oncotarget. 2017 Jan 17;8(3):4484-4500. doi: 10.18632/oncotarget.13152.
• [28] Polymorphism of the 3'-untranslated region of interleukin-12 p40 gene is not associated with the presence or severity of coronary artery disease.Circ J. 2005 Jul;69(7):793-7. doi: 10.1253/circj.69.793.
• [29] Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1296-305. doi: 10.1073/pnas.1513801113. Epub 2016 Feb 16.
• [30] Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia.Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2145-50. doi: 10.1073/pnas.040569197.
• [31] Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression.J Am Acad Dermatol. 2017 Jan;76(1):91-97.e3. doi: 10.1016/j.jaad.2016.07.047. Epub 2016 Oct 13.
• [32] Production of a Functional Factor, p40, by Lactobacillus rhamnosus GG Is Promoted by Intestinal Epithelial Cell-Secreted Extracellular Vesicles.Infect Immun. 2019 Jun 20;87(7):e00113-19. doi: 10.1128/IAI.00113-19. Print 2019 Jul.
• [33] miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42 axis.J Exp Clin Cancer Res. 2018 Mar 27;37(1):71. doi: 10.1186/s13046-018-0729-z.
• [34] Evaluation of the endoplasmic reticulum-stress response in eIF2B-mutated lymphocytes and lymphoblasts from CACH/VWM patients.BMC Neurol. 2010 Oct 19;10:94. doi: 10.1186/1471-2377-10-94.
• [35] American Registry of Pathology Expert Opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.Ann Diagn Pathol. 2020 Feb;44:151419. doi: 10.1016/j.anndiagpath.2019.151419. Epub 2019 Nov 15.
• [36] Non-small cell lung carcinoma with diffuse coexpression of thyroid transcription factor-1 and Np63/p40.Hum Pathol. 2018 Aug;78:177-181. doi: 10.1016/j.humpath.2018.01.023. Epub 2018 Feb 2.
• [37] Alleles of the IL12B 3'UTR associate with late onset of type 1 diabetes.Hum Immunol. 2004 Dec;65(12):1432-6. doi: 10.1016/j.humimm.2004.09.001.
• [38] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [39] 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.
• [40] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [41] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [42] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [43] 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.
• [44] 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.
• [45] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [46] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [47] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [48] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [49] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [50] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [51] Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin. Am J Respir Cell Mol Biol. 2004 May;30(5):662-70. doi: 10.1165/rcmb.2003-0267OC. Epub 2003 Nov 20.
• [52] Flubendazole and mebendazole impair migration and epithelial to mesenchymal transition in oral cell lines. Chem Biol Interact. 2018 Sep 25;293:124-132. doi: 10.1016/j.cbi.2018.07.026. Epub 2018 Jul 31.
• [53] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [54] 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.
• [55] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [56] 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.
• [57] 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.
• [58] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [59] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [60] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [61] 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.