Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0530 Transporter Info
Gene Name CACNA1H
Transporter Name Voltage-gated calcium channel alpha Cav3.2
Gene ID
8912
UniProt ID
O95180
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Mibefradil inhibits the reaction CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Cisplatin co-treated with jinfukang results in decreased expression of CACNA1H mRNA [6]

Regulation Mechanism

 Transcription Factor Info

  11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid

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

  DT Modulation1

 Cannabinoids results in increased abundance of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid which affects the methylation of CACNA1H gene [20]

Regulation Mechanism

 Transcription Factor Info

  1,6-hexamethylene diisocyanate

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

  DT Modulation1

 1,6-hexamethylene diisocyanate results in increased methylation of CACNA1H gene [21]

Regulation Mechanism

 Transcription Factor Info

  4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid

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

  DT Modulation1

 4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid results in increased expression of CACNA1H mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  abrine

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

  DT Modulation1

 abrine results in decreased expression of CACNA1H mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  Amiloride

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

  DT Modulation1

 Amiloride inhibits the reaction CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

  Barium

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

  DT Modulation1

 CACNA1H mRNA alternative form results in increased transport of Barium [26]

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 affects the methylation of CACNA1H exon [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene affects the methylation of CACNA1H promoter [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of CACNA1H 5' UTR [27]

Regulation Mechanism

 Transcription Factor Info

  benzo(e)pyrene

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

  DT Modulation1

 benzo(e)pyrene results in increased methylation of CACNA1H intron [23]

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 results in decreased methylation of CACNA1H gene [28]

Regulation Mechanism

 Transcription Factor Info

  Cannabinoids

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

  DT Modulation1

 Cannabinoids results in increased abundance of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid which affects the methylation of CACNA1H gene [20]

Regulation Mechanism

 Transcription Factor Info

  dicrotophos

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

  DT Modulation1

 dicrotophos results in increased expression of CACNA1H mRNA [17]

Regulation Mechanism

 Transcription Factor Info

  herbimycin

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

  DT Modulation1

 herbimycin results in increased activity of CACNA1H protein [29]

Regulation Mechanism

 Transcription Factor Info

  ICG 001

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

  DT Modulation1

 ICG 001 results in increased expression of CACNA1H mRNA [16]

Regulation Mechanism

 Transcription Factor Info

  Methapyrilene

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

  DT Modulation1

 Methapyrilene results in increased methylation of CACNA1H intron [23]

Regulation Mechanism

 Transcription Factor Info

  N-acetyl-4-benzoquinoneimine

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

  DT Modulation1

 CACNA1H gene SNP affects the susceptibility to N-acetyl-4-benzoquinoneimine [30]

Regulation Mechanism

 Transcription Factor Info

  Niclosamide

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

  DT Modulation1

 Niclosamide results in increased expression of CACNA1H mRNA [31]

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 CACNA1H mRNA [32]

Regulation Mechanism

 Transcription Factor Info

  oxophenylarsine

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

  DT Modulation1

 oxophenylarsine results in decreased activity of CACNA1H protein [29]

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 affects the methylation of CACNA1H gene [33]

Regulation Mechanism

 Transcription Factor Info

  Tetrachlorodibenzodioxin

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

  DT Modulation1

 Tetrachlorodibenzodioxin affects the expression of CACNA1H mRNA [15]

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 CACNA1H mRNA [34]

Regulation Mechanism

 Transcription Factor Info

  tyrphostin 47

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

  DT Modulation1

 tyrphostin 47 results in increased activity of CACNA1H protein [29]

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 CACNA1H gene [35]

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 affects the methylation of CACNA1H intron [23]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Arsenic

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

  DT Modulation1

 Arsenic affects the methylation of CACNA1H gene [25]

Regulation Mechanism

 Transcription Factor Info

  Nickel

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

  DT Modulation1

 Nickel inhibits the reaction CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

Dietary Constituent

  Calcium

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

  DT Modulation1

 Amiloride inhibits the reaction CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Mibefradil inhibits the reaction CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 Nickel inhibits the reaction CACNA1H protein results in increased transport of Calcium [24]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Cyclosporine

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

  DT Modulation1

 Cyclosporine increases the expression of CACNA1H [4]

  Menthol

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

  DT Modulation1

 Menthol inhibits the expression of CACNA1H [5]

  Cisplatin

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

  DT Modulation1

 Cisplatin inhibits the expression of CACNA1H [6]

  Leflunomide

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

  DT Modulation1

 Leflunomide increases the expression of CACNA1H [7]

  Doxorubicin

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

  DT Modulation1

 Doxorubicin inhibits the expression of CACNA1H [8]

  Sunitinib

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

  DT Modulation1

 Sunitinib increases the expression of CACNA1H [10]

  Flunarizine

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

  DT Modulation1

 Flunarizine blocks the activity of CACNA1H [11], [12]

  Sodium bicarbonate

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

  DT Modulation1

 Sodium bicarbonate blocks the activity of CACNA1H [13]

  Propafenone

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

  DT Modulation1

 Propafenone inhibits the activity of CACNA1H [14]

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 increases the expression of CACNA1H [9]

Drug in Phase 3 Trial

  Triclosan

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

  DT Modulation1

 Triclosan increases the expression of CACNA1H [18]

Drug in Phase 2 Trial

  ABT-639

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

  DT Modulation1

 ABT-639 modulates the activity of CACNA1H [19]

Drug in Phase 1 Trial

  Mibefradil

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

  DT Modulation1

 Mibefradil inhibits the activity of CACNA1H [1], [2]

Cell System

 Oocytes-CACNA1H

  DT Modulation2

 Mibefradil inhibits the activity of CACNA1H [3]

Cell System

 Human embryonic kidney 293 cells (HEK293)-CACNA1H

Patented Pharmaceutical Agent

  ICG-001

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

  DT Modulation1

 ICG-001 increases the expression of CACNA1H [16]

Environmental toxicant

  Polychlorinated dibenzodioxin

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

  DT Modulation1

 Polychlorinated dibenzodioxin affects the expression of CACNA1H [15]

Pesticide/Insecticide

  Dicrotophos

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

  DT Modulation1

 Dicrotophos increases the expression of CACNA1H [17]
References
1 3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.
2 Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2005 Jan 17;15(2):283-6.
3 Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 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.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
8 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.
9 Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone. Arch Toxicol. 2018 Aug;92(8):2587-2606.
10 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.
11 Migraine prophylaxis with calcium antagonists: a haemodynamic study using transcranial Doppler ultrasound. Rev Neurol. 2004 Feb 16-29;38(4):316-9.
12 Positive Allosteric Interaction of Structurally Diverse T-Type Calcium Channel Antagonists. Cell Biochem Biophys. 2009 Jul 7.
13 Acute renal failure. Clin Evid (Online). 2008 Sep 3;2008.
14 Optimization of propafenone analogues as antimalarial leads. J Med Chem. 2011 Nov 10;54(21):7477-85.
15 Cross-species comparisons of transcriptomic alterations in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2012 May;127(1):199-215.
16 Altering cancer transcriptomes using epigenomic inhibitors. Epigenetics Chromatin. 2015 Feb 24;8:9.
17 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
18 Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
19 Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. Pain. 2015 Nov;156(11):2175-83.
20 Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018;13(12):1208-1221.
21 DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014;231(2):217-26.
22 Integration of transcriptomics, proteomics and metabolomics data to reveal the biological mechanisms of abrin injury in human lung epithelial cells. Toxicol Lett. 2019;312:1-10.
23 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
24 Structure and functional characterization of a novel human low-voltage activated calcium channel. J Neurochem. 1999;72(2):791-9.
25 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.
26 Functional coupling between 'R-type' Ca2+ channels and insulin secretion in the insulinoma cell line INS-1. Eur J Biochem. 2001;268(4):1066-75.
27 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
28 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
29 Regulation of CA(v)3.2 Ca2+ channel activity by protein tyrosine phosphorylation. J Microbiol Biotechnol. 2008;18(2):365-8.
30 Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011;120(1):33-41.
31 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023;83(2):181-194.
32 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
33 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.
34 Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq. Toxicol In Vitro. 2018;46:178-188.
35 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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