Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBCIBC7)

• DOT Name: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1)
• Synonyms: dNTPase; EC 3.1.5.-; Dendritic cell-derived IFNG-induced protein; DCIP; Monocyte protein 5; MOP-5; SAM domain and HD domain-containing protein 1; hSAMHD1
• Gene Name: SAMHD1
• Related Disease:
  Aicardi-Goutieres syndrome 5
  T lymphoblastic leukaemia
  Acute monocytic leukemia
  Advanced cancer
  Anemia
  Arterial disorder
  Autoimmune disease
  Cerebrovascular disease
  Chikungunya virus infection
  Chilblain lupus 1
  CINCA syndrome
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cytomegalovirus infection
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Herpes simplex infection
  HIV infectious disease
  Immunodeficiency
  Lentivirus infection
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Mitochondrial DNA depletion syndrome, hepatocerebral form
  Moyamoya disease
  Neoplasm
  Primary cutaneous T-cell lymphoma
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
  Werner syndrome
  Encephalitis
  Inflammation
  Peripheral sensory neuropathies
  Aicardi-Goutieres syndrome
  Familial chilblain lupus
  Chilblain lupus
  Aicardi-Goutieres syndrome 1
  Aicardi-Goutieres syndrome 2
  Arthropathy
  Carcinoma of liver and intrahepatic biliary tract
  Chilblain lupus 2
  Dystonia
  Enterovirus infection
  Hepatitis B virus infection
  Liver cancer
  Pseudo-TORCH syndrome
  Stroke
  Vascular disease
• UniProt ID: SAMH1_HUMAN
• PDB ID: 2E8O ; 3U1N ; 4BZB ; 4BZC ; 4CC9 ; 4MZ7 ; 4Q7H ; 4QFX ; 4QFY ; 4QFZ ; 4QG0 ; 4QG1 ; 4QG2 ; 4QG4 ; 4RXO ; 4RXP ; 4RXQ ; 4RXR ; 4RXS ; 4TNP ; 4TNQ ; 4TNR ; 4TNX ; 4TNY ; 4TNZ ; 4TO0 ; 4TO1 ; 4TO2 ; 4TO3 ; 4TO4 ; 4TO5 ; 4TO6 ; 4ZWE ; 4ZWG ; 5AO0 ; 5AO1 ; 5AO2 ; 5AO3 ; 5AO4 ; 6CM2 ; 6DW3 ; 6DW4 ; 6DW5 ; 6DW7 ; 6DWD ; 6DWJ ; 6DWK ; 6TX0 ; 6TXA ; 6TXC ; 6TXE ; 6TXF ; 6U6X ; 6U6Y ; 6U6Z ; 6XU1 ; 6YOM ; 7A5Y ; 7LTT ; 7LU5 ; 7S2Y ; 7UJN ; 8D94 ; 8D9J ; 8GB1 ; 8GB2 ; 8TDW
• EC Number: 3.1.5.-
• Pfam ID: PF01966 ; PF07647
• Sequence:
  MQRADSEQPSKRPRCDDSPRTPSNTPSAEADWSPGLELHPDYKTWGPEQVCSFLRRGGFE
  EPVLLKNIRENEITGALLPCLDESRFENLGVSSLGERKKLLSYIQRLVQIHVDTMKVIND
  PIHGHIELHPLLVRIIDTPQFQRLRYIKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVH
  ALGEKQPELQISERDVLCVQIAGLCHDLGHGPFSHMFDGRFIPLARPEVKWTHEQGSVMM
  FEHLINSNGIKPVMEQYGLIPEEDICFIKEQIVGPLESPVEDSLWPYKGRPENKSFLYEI
  VSNKRNGIDVDKWDYFARDCHHLGIQNNFDYKRFIKFARVCEVDNELRICARDKEVGNLY
  DMFHTRNSLHRRAYQHKVGNIIDTMITDAFLKADDYIEITGAGGKKYRISTAIDDMEAYT
  KLTDNIFLEILYSTDPKLKDAREILKQIEYRNLFKYVGETQPTGQIKIKREDYESLPKEV
  ASAKPKVLLDVKLKAEDFIVDVINMDYGMQEKNPIDHVSFYCKTAPNRAIRITKNQVSQL
  LPEKFAEQLIRVYCKKVDRKSLYAARQYFVQWCADRNFTKPQDGDVIAPLITPQKKEWND
  STSVQNPTRLREASKSRVQLFKDDPM
• Function: Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks. Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells. Likewise, suppresses LINE-1 retrotransposon activity. Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx. In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools. Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks. Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication. Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation. Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity. Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation.
• Tissue Specificity: Expressed in heart, skeletal muscle, spleen, liver, small intestine, placenta, lung and peripheral blood leukocytes . No expression is seen in brain and thymus .
• KEGG Pathway:
  Viral life cycle - HIV-1 (hsa03250)
  Cytosolic D.-sensing pathway (hsa04623)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Nucleotide catabolism (R-HSA-8956319)

Molecular Interaction Atlas (MIA) of This DOT

52 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aicardi-Goutieres syndrome 5	DISU0BME	Definitive	Autosomal recessive	[1]
T lymphoblastic leukaemia	DIS2PNPP	Definitive	Biomarker	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Anemia	DISTVL0C	Strong	Genetic Variation	[5]
Arterial disorder	DISLG4XS	Strong	Genetic Variation	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Cerebrovascular disease	DISAB237	Strong	Genetic Variation	[8]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[9]
Chilblain lupus 1	DISEBS1O	Strong	Biomarker	[10]
CINCA syndrome	DISU6RZC	Strong	Genetic Variation	[11]
Colon cancer	DISVC52G	Strong	Genetic Variation	[12]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[17]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[18]
Immunodeficiency	DIS093I0	Strong	Biomarker	[19]
Lentivirus infection	DISX17PY	Strong	Biomarker	[20]
leukaemia	DISS7D1V	Strong	Biomarker	[3]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Posttranslational Modification	[21]
Lung cancer	DISCM4YA	Strong	Altered Expression	[22]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[22]
Lung neoplasm	DISVARNB	Strong	Biomarker	[21]
Mitochondrial DNA depletion syndrome, hepatocerebral form	DISXOJLH	Strong	Biomarker	[23]
Moyamoya disease	DISO62CA	Strong	Autosomal recessive	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[25]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[27]
Werner syndrome	DISZY45W	Strong	Genetic Variation	[28]
Encephalitis	DISLD1RL	moderate	Biomarker	[29]
Inflammation	DISJUQ5T	moderate	Genetic Variation	[30]
Peripheral sensory neuropathies	DISYWI6M	moderate	Genetic Variation	[31]
Aicardi-Goutieres syndrome	DIS1NH4X	Supportive	Autosomal dominant	[32]
Familial chilblain lupus	DISOSPDL	Supportive	Autosomal dominant	[10]
Chilblain lupus	DIS5792K	Disputed	Autosomal dominant	[33]
Aicardi-Goutieres syndrome 1	DISPAXC2	Limited	Biomarker	[34]
Aicardi-Goutieres syndrome 2	DISOL1R1	Limited	Biomarker	[34]
Arthropathy	DISVEERK	Limited	Genetic Variation	[11]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Genetic Variation	[35]
Chilblain lupus 2	DIS5R8J9	Limited	Autosomal dominant	[1]
Dystonia	DISJLFGW	Limited	Biomarker	[36]
Enterovirus infection	DISH2UDP	Limited	Biomarker	[37]
Hepatitis B virus infection	DISLQ2XY	Limited	Posttranslational Modification	[16]
Liver cancer	DISDE4BI	Limited	Genetic Variation	[35]
Pseudo-TORCH syndrome	DISM9N8Y	Limited	Biomarker	[34]
Stroke	DISX6UHX	Limited	Genetic Variation	[38]
Vascular disease	DISVS67S	Limited	Genetic Variation	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1) affects the binding of 4-hydroxy-2-nonenal.	[61]

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 Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[45]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[46]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[47]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[48]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[49]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[50]
Irinotecan	DMP6SC2	Approved	Irinotecan affects the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[51]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[53]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[54]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[55]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[59]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[60]

4 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 increases the sumoylation of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[56]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[58]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (SAMHD1).	[57]

References

• [1] 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.
• [2] SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia.Blood Cancer J. 2018 Jan 19;8(1):11. doi: 10.1038/s41408-017-0036-5.
• [3] Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML.Nat Commun. 2019 Aug 2;10(1):3475. doi: 10.1038/s41467-019-11413-4.
• [4] Defective modulation of LINE-1 retrotransposition by cancer-associated SAMHD1 mutants.Biochem Biophys Res Commun. 2019 Nov 5;519(2):213-219. doi: 10.1016/j.bbrc.2019.08.155. Epub 2019 Sep 4.
• [5] Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility.Virology. 2014 Jul;460-461:34-44. doi: 10.1016/j.virol.2014.04.023. Epub 2014 May 29.
• [6] Intracerebral large artery disease in Aicardi-Goutires syndrome implicates SAMHD1 in vascular homeostasis.Dev Med Child Neurol. 2010 Aug;52(8):725-32. doi: 10.1111/j.1469-8749.2010.03727.x.
• [7] SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity.Autoimmunity. 2018 May;51(3):96-110. doi: 10.1080/08916934.2018.1454912. Epub 2018 Mar 27.
• [8] SAMHD1 Gene Mutations Are Associated with Cerebral Large-Artery Atherosclerosis.Biomed Res Int. 2015;2015:739586. doi: 10.1155/2015/739586. Epub 2015 Oct 4.
• [9] SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts.Int J Mol Sci. 2019 Apr 5;20(7):1695. doi: 10.3390/ijms20071695.
• [10] Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis. 2017 Feb;76(2):468-472. doi: 10.1136/annrheumdis-2016-209841. Epub 2016 Aug 26.
• [11] Familial Aicardi-Goutires syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.Am J Med Genet A. 2010 Apr;152A(4):938-42. doi: 10.1002/ajmg.a.33359.
• [12] Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance.Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):4723-8. doi: 10.1073/pnas.1519128113. Epub 2016 Apr 11.
• [13] DNA-Sensing and Nuclease Gene Expressions as Markers for Colorectal Cancer Progression.Oncology. 2017;92(2):115-124. doi: 10.1159/000452281. Epub 2016 Dec 17.
• [14] A viral kinase counteracts in vivo restriction of murine cytomegalovirus by SAMHD1.Nat Microbiol. 2019 Dec;4(12):2273-2284. doi: 10.1038/s41564-019-0529-z. Epub 2019 Sep 23.
• [15] Genome-wide bioinformatics analysis reveals CTCFL is upregulated in high-grade epithelial ovarian cancer.Oncol Lett. 2019 Oct;18(4):4030-4039. doi: 10.3892/ol.2019.10736. Epub 2019 Aug 8.
• [16] Cyclin E2-CDK2 mediates SAMHD1 phosphorylation to abrogate its restriction of HBV replication in hepatoma cells.FEBS Lett. 2018 Jun;592(11):1893-1904. doi: 10.1002/1873-3468.13105. Epub 2018 Jun 6.
• [17] SAMHD1 restricts herpes simplex virus 1 in macrophages by limiting DNA replication.J Virol. 2013 Dec;87(23):12949-56. doi: 10.1128/JVI.02291-13. Epub 2013 Sep 25.
• [18] BCL6 Inhibitor-Mediated Downregulation of Phosphorylated SAMHD1 and T Cell Activation Are Associated with Decreased HIV Infection and Reactivation.J Virol. 2019 Jan 4;93(2):e01073-18. doi: 10.1128/JVI.01073-18. Print 2019 Jan 15.
• [19] Interplay of ancestral non-primate lentiviruses with the virus-restricting SAMHD1 proteins of their hosts.J Biol Chem. 2018 Oct 19;293(42):16402-16412. doi: 10.1074/jbc.RA118.004567. Epub 2018 Sep 4.
• [20] SAMHD1: a novel antiviral factor in intrinsic immunity.Future Microbiol. 2012 Sep;7(9):1117-26. doi: 10.2217/fmb.12.81.
• [21] SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation.Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):229-33. doi: 10.1016/j.bbrc.2014.10.153. Epub 2014 Nov 6.
• [22] Graphene Oxide-Facilitated Comprehensive Analysis of Cellular Nucleic Acid Binding Proteins for Lung Cancer.ACS Appl Mater Interfaces. 2018 May 30;10(21):17756-17770. doi: 10.1021/acsami.8b05428. Epub 2018 May 15.
• [23] The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase.J Biol Chem. 2015 Oct 23;290(43):25986-96. doi: 10.1074/jbc.M115.675082. Epub 2015 Sep 4.
• [24] 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.
• [25] MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Szary syndrome patients.Leuk Res. 2017 Jan;52:58-66. doi: 10.1016/j.leukres.2016.11.010. Epub 2016 Nov 17.
• [26] The missing link: allostery and catalysis in the anti-viral protein SAMHD1.Biochem Soc Trans. 2019 Aug 30;47(4):1013-1027. doi: 10.1042/BST20180348. Epub 2019 Jul 11.
• [27] SAMHD1 prevents autoimmunity by maintaining genome stability.Ann Rheum Dis. 2015 Mar;74(3):e17. doi: 10.1136/annrheumdis-2013-204845. Epub 2014 Jan 20.
• [28] Atypical Aicardi-Goutieres syndrome: is the WRN locus a modifier?.Am J Med Genet A. 2014 Oct;164A(10):2510-3. doi: 10.1002/ajmg.a.36664. Epub 2014 Jul 2.
• [29] Lentiviral infection of proliferating brain macrophages in HIV and simian immunodeficiency virus encephalitis despite sterile alpha motif and histidine-aspartate domain-containing protein 1 expression.AIDS. 2018 May 15;32(8):965-974. doi: 10.1097/QAD.0000000000001793.
• [30] SAMHD1 acts at stalled replication forks to prevent interferon induction.Nature. 2018 May;557(7703):57-61. doi: 10.1038/s41586-018-0050-1. Epub 2018 Apr 18.
• [31] Pharmacogenetic variation influences sensory neuropathy occurrence in Southern Africans treated with stavudine-containing antiretroviral therapy.PLoS One. 2018 Oct 1;13(10):e0204111. doi: 10.1371/journal.pone.0204111. eCollection 2018.
• [32] Aicardi-Goutires Syndrome. 2005 Jun 29 [updated 2016 Nov 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [33] Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. Am J Med Genet A. 2011 Jan;155A(1):235-7. doi: 10.1002/ajmg.a.33778.
• [34] Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction.J Biol Chem. 2013 Mar 22;288(12):8101-8110. doi: 10.1074/jbc.M112.431148. Epub 2013 Jan 30.
• [35] Identification of natural splice variants of SAMHD1 in virus-infected HCC.Oncol Rep. 2014 Feb;31(2):687-92. doi: 10.3892/or.2013.2895. Epub 2013 Dec 5.
• [36] Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutires syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression.Hum Mutat. 2010 Nov;31(11):E1836-50. doi: 10.1002/humu.21357.
• [37] TRIM21-mediated proteasomal degradation of SAMHD1 regulates its antiviral activity.EMBO Rep. 2020 Jan 7;21(1):e47528. doi: 10.15252/embr.201847528. Epub 2019 Dec 4.
• [38] Characterization of samhd1 morphant zebrafish recapitulates features of the human type I interferonopathy Aicardi-Goutires syndrome.J Immunol. 2015 Mar 15;194(6):2819-25. doi: 10.4049/jimmunol.1403157. Epub 2015 Feb 11.
• [39] Tocilizumab reverses cerebral vasculopathy in a patient with homozygous SAMHD1 mutation.Clin Rheumatol. 2017 Jun;36(6):1445-1451. doi: 10.1007/s10067-017-3600-2. Epub 2017 Mar 13.
• [40] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [41] 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.
• [42] 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.
• [43] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] 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.
• [46] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [47] 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.
• [48] 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.
• [49] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [50] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [51] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [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] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [54] 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.
• [55] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [56] 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.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [59] 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.
• [60] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [61] Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: protein carbonylation is diminished by ascorbic acid. Chem Res Toxicol. 2010 Jan;23(1):37-47. doi: 10.1021/tx9002462.