Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0528 Transporter Info
Gene Name SCN8A
Transporter Name Voltage-gated sodium channel alpha Nav1.6
Gene ID
6334
UniProt ID
O95788
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Cannabidiol results in decreased activity of SCN8A protein [2]

Regulation Mechanism

 Transcription Factor Info

  1-Methyl-3-isobutylxanthine

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol A results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol F results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NOG protein co-treated with p-Chloromercuribenzoic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SCN8A mRNA [9]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene results in increased methylation of SCN8A 5' UTR [11]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in increased methylation of SCN8A exon [11]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of SCN8A promoter [11]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol A results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  bisphenol F

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol F results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  Cadmium Chloride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cadmium Chloride results in decreased expression of SCN8A mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  Carmustine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 SCN8A mRNA affects the susceptibility to Carmustine [13]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to SCN8A gene [14]

Regulation Mechanism

 Transcription Factor Info

  Copper

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NSC 689534 binds to Copper which results in increased expression of SCN8A mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  decamethrin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 decamethrin affects the activity of SCN8A protein [6]

Regulation Mechanism

 Transcription Factor Info

  Dexamethasone

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol A results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol F results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  dorsomorphin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NOG protein co-treated with p-Chloromercuribenzoic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SCN8A mRNA [9]

Regulation Mechanism

 Transcription Factor Info

  Estradiol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Estradiol co-treated with TGFB1 protein results in increased expression of SCN8A mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  Indomethacin

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol A results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol F results in decreased expression of SCN8A mRNA [8]

Regulation Mechanism

 Transcription Factor Info

  NSC 689534

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NSC 689534 binds to Copper which results in increased expression of SCN8A mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  p-Chloromercuribenzoic Acid

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NOG protein co-treated with p-Chloromercuribenzoic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SCN8A mRNA [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 p-Chloromercuribenzoic Acid results in increased expression of SCN8A mRNA [17]

Regulation Mechanism

 Transcription Factor Info

  prothioconazole

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 prothioconazole results in decreased expression of SCN8A mRNA [18]

Regulation Mechanism

 Transcription Factor Info

  S-(1,2-dichlorovinyl)cysteine

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 S-(1,2-dichlorovinyl)cysteine affects the susceptibility to Lipopolysaccharides which results in increased expression of SCN8A mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 S-(1,2-dichlorovinyl)cysteine co-treated with Lipopolysaccharides results in increased expression of SCN8A mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 S-(1,2-dichlorovinyl)cysteine results in increased expression of SCN8A mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenite affects the methylation of SCN8A gene [20]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased expression of SCN8A mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  Temozolomide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 SCN8A mRNA affects the susceptibility to Temozolomide [13]

Regulation Mechanism

 Transcription Factor Info

  Valproic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Valproic Acid results in decreased methylation of SCN8A gene [22]

Regulation Mechanism

 Transcription Factor Info

Mycotoxins

  Aflatoxin B1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 results in increased methylation of SCN8A gene [10]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Melphalan

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Melphalan inhibits the expression of SCN8A [1]

  Cannabidiol

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cannabidiol inhibits the activity of SCN8A [2]

  Sunitinib

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sunitinib inhibits the expression of SCN8A [3]

  Tretinoin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tretinoin increases the expression of SCN8A [4]

Drug in Phase 2 Trial

  Genistein

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Genistein inhibits the expression of SCN8A [5]

Natural Product

  Tobacco Smoke Pollution

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tobacco Smoke Pollution inhibits the expression of SCN8A [7]

Pesticide/Insecticide

  Decamethrin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Decamethrin affects the activity of SCN8A [6]
References
1 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758.
2 Inhibitory effects of cannabidiol on voltage-dependent sodium currents. J Biol Chem. 2018 Oct 26;293(43):16546-16558.
3 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.
4 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
5 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
6 Effects of Deltamethrin Acute Exposure on Nav1.6 Channels and Medium Spiny Neurons of the Nucleus Accumbens. Toxicology. 2020 Jul;440:152488.
7 Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. 2021 May;95(5):1739-1761.
8 Low-dose exposure to bisphenols A, F and S of human primary adipocyte impacts coding and non-coding RNA profiles. PLoS One. 2017;12(6):e0179583.
9 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
10 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
11 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
12 Differential effect of the duration of exposure on the carcinogenicity of cadmium in MCF10A mammary epithelial cells. Food Chem Toxicol. 2024;186:114523.
13 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;24(2):274-87.
14 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
15 A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radic Biol Med. 2011 Jan 1;50(1):110-21.
16 Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells. Respir Res. 2018 Aug 30;19(1):160.
17 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.
18 Prothioconazole induces cell cycle arrest by up-regulation of EIF4EBP1 in extravillous trophoblast cells. Arch Toxicol. 2022;96(2):559-570.
19 The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model. Toxicol In Vitro. 2022;84:105429.
20 Microarray dataset of transient and permanent DNA methylation changes in HeLa cells undergoing inorganic arsenic-mediated epithelial-to-mesenchymal transition. Data Brief. 2017;13:6-9.
21 High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
22 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.

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