Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0527 Transporter Info
Gene Name SCN4A
Transporter Name Voltage-gated sodium channel alpha Nav1.4
Gene ID
6329
UniProt ID
P35499
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Cannabidiol results in decreased activity of SCN4A protein [2]

Regulation Mechanism

 Transcription Factor Info

  1-Methyl-4-phenylpyridinium

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

  DT Modulation1

 1-Methyl-4-phenylpyridinium results in increased expression of SCN4A mRNA [4]

Regulation Mechanism

 Transcription Factor Info

  2,6-xylenol

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

  DT Modulation1

 2,6-xylenol binds to and results in decreased activity of SCN4A protein [11]

Regulation Mechanism

 Transcription Factor Info

  2-methyl-4-chlorophenol

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

  DT Modulation1

 2-methyl-4-chlorophenol affects the activity of SCN4A protein polymorphism [3]

Regulation Mechanism

 Transcription Factor Info

  3-cresol

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

  DT Modulation1

 3-cresol affects the activity of SCN4A protein polymorphism [3]

Regulation Mechanism

 Transcription Factor Info

  4-chlorophenol

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

  DT Modulation1

 4-chlorophenol affects the activity of SCN4A protein polymorphism [3]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 4-chlorophenol binds to and results in decreased activity of SCN4A protein [11]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene results in decreased methylation of SCN4A exon [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in decreased methylation of SCN4A promoter [12]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

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

  DT Modulation1

 bisphenol A analog results in increased expression of SCN4A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 bisphenol A co-treated with Fulvestrant results in increased methylation of SCN4A gene [13]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 bisphenol A results in increased methylation of SCN4A gene [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 SCN4A gene [14]

Regulation Mechanism

 Transcription Factor Info

  chloroxylenol

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

  DT Modulation1

 chloroxylenol affects the activity of SCN4A protein polymorphism [3]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 chloroxylenol binds to and results in decreased activity of SCN4A protein [11]

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 decreased expression of SCN4A protein [8]

Regulation Mechanism

 Transcription Factor Info

  ethyl-p-hydroxybenzoate

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

  DT Modulation1

 ethyl-p-hydroxybenzoate results in decreased expression of SCN4A mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  fluorene-9-bisphenol

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

  DT Modulation1

 fluorene-9-bisphenol results in increased expression of SCN4A mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

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

  DT Modulation1

 bisphenol A co-treated with Fulvestrant results in increased methylation of SCN4A gene [13]

Regulation Mechanism

 Transcription Factor Info

  Lidocaine

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

  DT Modulation1

 Lidocaine binds to and results in decreased activity of SCN4A protein [11]

Regulation Mechanism

 Transcription Factor Info

  N-(2-methyl-3-(4-(4-(4-(trifluoromethoxy)benzyloxy)piperidin-1-yl)-1,3,5-triazin-2-ylamino)phenyl)acetamide

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

  DT Modulation1

 N-(2-methyl-3-(4-(4-(4-(trifluoromethoxy)benzyloxy)piperidin-1-yl)-1,3,5-triazin-2-ylamino)phenyl)acetamide results in decreased activity of SCN4A protein [17]

Regulation Mechanism

 Transcription Factor Info

  Okadaic Acid

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

  DT Modulation1

 Okadaic Acid results in increased expression of SCN4A mRNA [18]

Regulation Mechanism

 Transcription Factor Info

  pirinixic acid

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

  DT Modulation1

 pirinixic acid binds to and results in increased activity of PPARA protein which results in decreased expression of SCN4A mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  S-(1,2-dichlorovinyl)cysteine

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

  DT Modulation1

 S-(1,2-dichlorovinyl)cysteine inhibits the reaction Lipopolysaccharides results in decreased expression of SCN4A mRNA [20]

Regulation Mechanism

 Transcription Factor Info

  tri-o-cresyl phosphate

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

  DT Modulation1

 tri-o-cresyl phosphate results in increased expression of SCN4A mRNA [21]

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 increased methylation of SCN4A gene [22]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Troglitazone

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

  DT Modulation1

 Troglitazone increases the expression of SCN4A [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 SCN4A [2]

Drug in Phase 2 Trial

  Bisphenol A

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

  DT Modulation1

 Bisphenol A increases the expression of SCN4A [7]

Drug in Preclinical Test

  (+)-JQ1

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

  DT Modulation1

 (+)-JQ1 inhibits the expression of SCN4A [5]

Discontinued Drug

  Sipatrigine

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

  DT Modulation1

 Sipatrigine inhibits the activity of SCN4A [10]

Investigative Drug

  Chloroxylenol

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

  DT Modulation1

 Chloroxylenol affects the activity of SCN4A [3]

  Zrccncsskwcrdhsrcc

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

  DT Modulation1

 Zrccncsskwcrdhsrcc inhibits the activity of SCN4A [9]

Pesticide/Insecticide

  Cypermethrin

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

  DT Modulation1

 Cypermethrin inhibits the expression of SCN4A [8]

Health and Environmental Toxicant

  1-methyl-4-phenylpyridinium

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

  DT Modulation1

 1-methyl-4-phenylpyridinium increases the expression of SCN4A [4]

  Diethylhexyl Phthalate

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

  DT Modulation1

 Diethylhexyl Phthalate inhibits the expression of SCN4A [6]
References
1 Adipogenic Effects and Gene Expression Profiling of Firemaster?550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013.
2 Inhibitory effects of cannabidiol on voltage-dependent sodium currents. J Biol Chem. 2018 Oct 26;293(43):16546-16558.
3 Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel. Eur J Pharmacol. 2001 Mar 23;416(1-2):11-8.
4 Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+). Cell Death Dis. 2014 May 8;5(5):e1222.
5 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
6 Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPAR Gamma/PTEN/AKT pathway in differentiated human embryonic stem cells. Food Chem Toxicol. 2019 Sep;131:110552.
7 Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor alpha. Toxicol Appl Pharmacol. 2020 Jul 15;399:115030.
8 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.
9 Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem. 2007 Oct 19;282(42):30699-706.
10 Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
11 An improved model for the binding of lidocaine and structurally related local anaesthetics to fast-inactivated voltage-operated sodium channels, showing evidence of cooperativity. Br J Pharmacol. 2004;141(1):47-54.
12 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
14 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
15 Risk assessment of parabens in a transcriptomics-based in vitro test. Chem Biol Interact. 2023;384:110699.
16 Integrated analysis reveals the immunotoxicity mechanism of BPs on human lymphocytes. Chem Biol Interact. 2024;399:111148.
17 Identification of a potent, state-dependent inhibitor of Nav1.7 with oral efficacy in the formalin model of persistent pain. J Med Chem. 2011;54(13):4427-45.
18 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
19 Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One. 2009;4(8):e6796.
20 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.
21 Organophosphate ester tri-o-cresyl phosphate interacts with estrogen receptor in MCF-7 breast cancer cells promoting cancer growth. Toxicol Appl Pharmacol. 2020;395:114977.
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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