Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVLI4DD)

• DOT Name: Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)
• Synonyms: TNF alpha-induced protein 3; EC 2.3.2.-; EC 3.4.19.12; OTU domain-containing protein 7C; Putative DNA-binding protein A20; Zinc finger protein A20
• Gene Name: TNFAIP3
• Related Disease:
  Autoinflammatory syndrome, familial, Behcet-like 1
  Obsolete hereditary pediatric Behet-like disease
• UniProt ID: TNAP3_HUMAN
• PDB ID: 2EQE; 2EQF; 2EQG; 2VFJ; 3DKB; 3OJ3; 3OJ4; 3VUW; 3VUX; 3VUY; 3ZJD; 3ZJE; 3ZJF; 3ZJG; 5LRX; 5V3B; 5V3P
• EC Number: 2.3.2.-; 3.4.19.12
• Pfam ID: PF02338 ; PF01754
• Sequence:
  MAEQVLPQALYLSNMRKAVKIRERTPEDIFKPTNGIIHHFKTMHRYTLEMFRTCQFCPQF
  REIIHKALIDRNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDL
  VLRKALFSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLIKMASTDTP
  MARSGLQYNSLEEIHIFVLCNILRRPIIVISDKMLRSLESGSNFAPLKVGGIYLPLHWPA
  QECYRYPIVLGYDSHHFVPLVTLKDSGPEIRAVPLVNRDRGRFEDLKVHFLTDPENEMKE
  KLLKEYLMVIEIPVQGWDHGTTHLINAAKLDEANLPKEINLVDDYFELVQHEYKKWQENS
  EQGRREGHAQNPMEPSVPQLSLMDVKCETPNCPFFMSVNTQPLCHECSERRQKNQNKLPK
  LNSKPGPEGLPGMALGASRGEAYEPLAWNPEESTGGPHSAPPTAPSPFLFSETTAMKCRS
  PGCPFTLNVQHNGFCERCHNARQLHASHAPDHTRHLDPGKCQACLQDVTRTFNGICSTCF
  KRTTAEASSSLSTSLPPSCHQRSKSDPSRLVRSPSPHSCHRAGNDAPAGCLSQAARTPGD
  RTGTSKCRKAGCVYFGTPENKGFCTLCFIEYRENKHFAAASGKVSPTASRFQNTIPCLGR
  ECGTLGSTMFEGYCQKCFIEAQNQRFHEAKRTEEQLRSSQRRDVPRTTQSTSRPKCARAS
  CKNILACRSEELCMECQHPNQRMGPGAHRGEPAPEDPPKQRCRAPACDHFGNAKCNGYCN
  ECFQFKQMYG
• Function: Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages.
• KEGG Pathway:
  NF-kappa B sig.ling pathway (hsa04064)
  Necroptosis (hsa04217)
  NOD-like receptor sig.ling pathway (hsa04621)
  IL-17 sig.ling pathway (hsa04657)
  TNF sig.ling pathway (hsa04668)
  Measles (hsa05162)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  TNFR1-induced proapoptotic signaling (R-HSA-5357786)
  Regulation of TNFR1 signaling (R-HSA-5357905)
  TNFR1-induced NF-kappa-B signaling pathway (R-HSA-5357956)
  Ovarian tumor domain proteases (R-HSA-5689896)
  Negative regulators of DDX58/IFIH1 signaling (R-HSA-936440)
  NOD1/2 Signaling Pathway (R-HSA-168638)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoinflammatory syndrome, familial, Behcet-like 1	DISH2UT1	Strong	Autosomal dominant	[1]
Obsolete hereditary pediatric Behet-like disease	DISNNKF2	Moderate	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) increases the response to substance of DTI-015.	[56]

69 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 Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[15]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[19]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[20]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[21]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[22]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[23]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[24]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[25]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[26]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[27]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[28]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[29]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[30]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[31]
Clonidine	DM6RZ9Q	Approved	Clonidine increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Ibrutinib	DMHZCPO	Approved	Ibrutinib decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[32]
Tolbutamide	DM02AWV	Approved	Tolbutamide decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Mannitol	DMSCDY9	Approved	Mannitol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[33]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[34]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[35]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[31]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[31]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[36]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[12]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[25]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[9]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[38]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[39]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[41]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[43]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[45]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[46]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[47]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[48]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[49]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[50]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[51]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[52]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[53]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[18]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[31]
Choline	DM5D9YK	Investigative	Choline affects the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[54]
Fenthion	DMKEG49	Investigative	Fenthion increases the expression of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Tumor necrosis factor alpha-induced protein 3 (TNFAIP3).	[42]

References

• [1] Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016 Jan;48(1):67-73. doi: 10.1038/ng.3459. Epub 2015 Dec 7.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
• [10] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [11] 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.
• [12] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] Peripheral blood expression of nuclear factor-kappab-regulated genes is associated with rheumatoid arthritis disease activity and responds differentially to anti-tumor necrosis factor-alpha versus methotrexate. J Rheumatol. 2007 Sep;34(9):1817-22. Epub 2007 Aug 1.
• [16] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity. Toxicol Sci. 2011 Dec;124(2):278-90. doi: 10.1093/toxsci/kfr225. Epub 2011 Aug 27.
• [19] Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [22] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [23] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [24] Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
• [25] Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytes. J Biochem Mol Toxicol. 2010 Jan-Feb;24(1):10-20.
• [26] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [27] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [28] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [29] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [30] The hepatotoxic fluoroquinolone trovafloxacin disturbs TNF- and LPS-induced p65 nuclear translocation in vivo and in vitro. Toxicol Appl Pharmacol. 2020 Mar 15;391:114915. doi: 10.1016/j.taap.2020.114915. Epub 2020 Feb 6.
• [31] Mapping the dynamics of Nrf2 antioxidant and NFB inflammatory responses by soft electrophilic chemicals in human liver cells defines the transition from adaptive to adverse responses. Toxicol In Vitro. 2022 Oct;84:105419. doi: 10.1016/j.tiv.2022.105419. Epub 2022 Jun 17.
• [32] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [33] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [34] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [35] Effects of resveratrol on gene expression in renal cell carcinoma. Cancer Biol Ther. 2004 Sep;3(9):882-8. doi: 10.4161/cbt.3.9.1056. Epub 2004 Sep 21.
• [36] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [37] 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.
• [38] 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.
• [39] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [40] Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):272-7. doi: 10.1073/pnas.1008969108. Epub 2010 Dec 20.
• [41] 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.
• [42] 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.
• [43] Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes. Toxicol Lett. 2010 Nov 10;199(1):51-9.
• [44] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [45] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [46] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [47] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [48] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [49] 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.
• [50] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [51] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [52] 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.
• [53] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
• [54] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.
• [55] Fenthion and terbufos induce DNA damage, the expression of tumor-related genes, and apoptosis in HEPG2 cells. Environ Mol Mutagen. 2011 Aug;52(7):529-37. doi: 10.1002/em.20652. Epub 2011 Apr 27.
• [56] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.