Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0526 Transporter Info
Gene Name SCN1A
Transporter Name Voltage-gated sodium channel alpha Nav1.1
Gene ID
6323
UniProt ID
P35498
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Cannabidiol results in decreased activity of SCN1A protein [8]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 NOG protein co-treated with Valproic 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 SCN1A mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Valproic Acid affects the expression of SCN1A mRNA [31]

Regulation Mechanism

 Transcription Factor Info

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

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

  DT Modulation1

 NOG protein co-treated with trichostatin A 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 SCN1A mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NOG protein co-treated with Valproic 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 SCN1A mRNA [5]

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

 bisphenol A affects the expression of SCN1A mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Carbamazepine

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

  DT Modulation1

 SCN1A gene polymorphism results in decreased susceptibility to Carbamazepine [22]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 SCN1A protein affects the susceptibility to Carbamazepine [23]

Regulation Mechanism

 Transcription Factor Info

  cypermethrin

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

  DT Modulation1

 cypermethrin results in increased expression of SCN1A protein [16]

Regulation Mechanism

 Transcription Factor Info

  Diethylhexyl Phthalate

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

  DT Modulation1

 Diethylhexyl Phthalate results in increased expression of SCN1A mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  dorsomorphin

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

  DT Modulation1

 NOG protein co-treated with trichostatin A 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 SCN1A mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NOG protein co-treated with Valproic 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 SCN1A mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  entinostat

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

  DT Modulation1

 entinostat results in increased expression of SCN1A mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

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

  DT Modulation1

 Fulvestrant results in increased methylation of SCN1A gene [26]

Regulation Mechanism

 Transcription Factor Info

  perfluorohexanesulfonic acid

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

  DT Modulation1

 perfluorohexanesulfonic acid results in increased expression of SCN1A mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  perfluorooctane sulfonic acid

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

  DT Modulation1

 perfluorooctane sulfonic acid results in increased expression of SCN1A mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  perfluorooctanoic acid

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

  DT Modulation1

 perfluorooctanoic acid results in increased expression of SCN1A mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  Phenytoin

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

  DT Modulation1

 SCN1A gene polymorphism affects the susceptibility to Phenytoin [28]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 SCN1A protein affects the susceptibility to Phenytoin [23]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

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

  DT Modulation1

 sodium arsenite results in increased expression of SCN1A mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  sulforaphane

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

  DT Modulation1

 sulforaphane results in decreased expression of SCN1A mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  Tetrachlorodibenzodioxin

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

  DT Modulation1

 Endosulfan inhibits the reaction Tetrachlorodibenzodioxin results in increased expression of SCN1A mRNA [25]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Tetrachlorodibenzodioxin results in decreased expression of SCN1A mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Tetrachlorodibenzodioxin results in increased expression of SCN1A mRNA [25]

Regulation Mechanism

 Transcription Factor Info

  trichostatin A

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

  DT Modulation1

 NOG protein co-treated with trichostatin A 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 SCN1A mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 trichostatin A inhibits the reaction Nickel affects the expression of SCN1A mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 trichostatin A results in increased expression of SCN1A mRNA [29]

Regulation Mechanism

 Transcription Factor Info

  tris(2-butoxyethyl) phosphate

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

  DT Modulation1

 tris(2-butoxyethyl) phosphate affects the expression of SCN1A mRNA [30]

Regulation Mechanism

 Transcription Factor Info

Nanoparticle

  perfluoro-n-nonanoic acid

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

  DT Modulation1

 perfluoro-n-nonanoic acid results in increased expression of SCN1A mRNA [11]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Copper Sulfate

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

  DT Modulation1

 Copper Sulfate inhibits the expression of SCN1A [1]

  Tretinoin

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

  DT Modulation1

 Tretinoin inhibits the expression of SCN1A [2]

  Azathioprine

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

  DT Modulation1

 Azathioprine inhibits the expression of SCN1A [3]

  Cyclosporine

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

  DT Modulation1

 Cyclosporine inhibits the expression of SCN1A [4]

  Vorinostat

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

  DT Modulation1

 Vorinostat increases the expression of SCN1A [5]

  Urethane

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

  DT Modulation1

 Urethane inhibits the expression of SCN1A [6]

  Cannabidiol

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

  DT Modulation1

 Cannabidiol inhibits the activity of SCN1A [8]

  Estradiol

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

  DT Modulation1

 Estradiol inhibits the expression of SCN1A [9]

  Valproic Acid

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

  DT Modulation1

 Valproic Acid increases the expression of SCN1A [10]

Drug Marketed but not Approved by US FDA

  Rotenone

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

  DT Modulation1

 Rotenone inhibits the expression of SCN1A [7]

Drug in Phase 3 Trial

  Sulforafan

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

  DT Modulation1

 Sulforafan inhibits the expression of SCN1A [14]

Drug in Phase 2 Trial

  MS-275

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

  DT Modulation1

 MS-275 increases the expression of SCN1A [5]

  Bisphenol A

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

  DT Modulation1

 Bisphenol A affects the expression of SCN1A [13]

Drug in Phase 1 Trial

  Quercetin

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

  DT Modulation1

 Quercetin inhibits the expression of SCN1A [9]

  Sodium arsenite

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

  DT Modulation1

 Sodium arsenite increases the expression of SCN1A [12]

  Trichostatin A

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

  DT Modulation1

 Trichostatin A increases the expression of SCN1A [5]

Investigative Drug

  Batrachotoxin

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

  DT Modulation1

 Batrachotoxin activates the activity of SCN1A [18]

  Veratridine

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

  DT Modulation1

 Veratridine activates the activity of SCN1A [18]

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 SCN1A [15]

Environmental toxicant

  Polychlorinated dibenzodioxin

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

  DT Modulation1

 Polychlorinated dibenzodioxin inhibits the expression of SCN1A [9]

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 inhibits the expression of SCN1A [9]

  DT Modulation2

 Aflatoxin B1 affects the expression of SCN1A protein [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Aflatoxin B1 results in increased expression of SCN1A mRNA [20]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SCN1A [17]

  Arsenic

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

  DT Modulation1

 Arsenic affects the methylation of SCN1A gene [21]

Regulation Mechanism

 Transcription Factor Info

  Nickel

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

  DT Modulation1

 Nickel affects the expression of SCN1A mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 trichostatin A inhibits the reaction Nickel affects the expression of SCN1A mRNA [27]

Regulation Mechanism

 Transcription Factor Info

Pesticide/Insecticide

  Cypermethrin

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

  DT Modulation1

 Cypermethrin increases the expression of SCN1A [16]

Health and Environmental Toxicant

  Perfluorooctane sulfonic acid

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

  DT Modulation1

 Perfluorooctane sulfonic acid increases the expression of SCN1A [11]

  Endosulfan

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

  DT Modulation1

 Endosulfan inhibits the reaction Tetrachlorodibenzodioxin results in increased expression of SCN1A mRNA [25]

Regulation Mechanism

 Transcription Factor Info
References
1 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
2 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
3 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 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.
6 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
7 Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone. Arch Toxicol. 2018 Aug;92(8):2587-2606.
8 Inhibitory effects of cannabidiol on voltage-dependent sodium currents. J Biol Chem. 2018 Oct 26;293(43):16546-16558.
9 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.
10 Stem Cell Transcriptome Responses and Corresponding Biomarkers That Indicate the Transition from Adaptive Responses to Cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
11 Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood. J Immunotoxicol. 2016;13(2):173-80.
12 Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
13 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134.
14 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.
15 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.
16 Proteomic profiling reveals neuronal ion channel dysregulation and cellular responses to DNA damage-induced cell cycle arrest and senescence in human neuroblastoma SH-SY5Y cells exposed to cypermethrin. Neurotoxicology. 2022 Dec;93:71-83.
17 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
18 Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 578).
19 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.
20 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
21 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.
22 Association between SCN1A polymorphism and carbamazepine-resistant epilepsy. Br J Clin Pharmacol. 2008;66(2):304-7.
23 Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12.
24 Korean Red Ginseng attenuates Di-(2-ethylhexyl) phthalate-induced inflammatory response in endometrial cancer cells and an endometriosis mouse model. J Ginseng Res. 2022;46(4):592-600.
25 Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism. Biochimie. 2015 Sep;116:79-91.
26 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
27 Inhibition and reversal of nickel-induced transformation by the histone deacetylase inhibitor trichostatin A. Toxicol Appl Pharmacol. 2003;192(3):201-11.
28 A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006 Oct;16(10):721-6.
29 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.
30 Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq. Toxicol In Vitro. 2018;46:178-188.
31 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20.

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