Details of Drug Off-Target (DOT)

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

• DOT Name: Endothelin-1 (EDN1)
• Synonyms: Preproendothelin-1; PPET1
• Gene Name: EDN1
• Related Disease:
  Auriculocondylar syndrome 1
  Auriculocondylar syndrome 3
  Question mark ears, isolated
  Auriculocondylar syndrome
• UniProt ID: EDN1_HUMAN
• PDB ID: 1EDN; 1EDP; 1T7H; 1V6R; 5GLH; 6DK5; 8HCQ; 8HCX; 8IY5; 8IY6
• Pfam ID: PF00322
• Sequence:
  MDYLLMIFSLLFVACQGAPETAVLGAELSAVGENGGEKPTPSPPWRLRRSKRCSCSSLMD
  KECVYFCHLDIIWVNTPEHVVPYGLGSPRSKRALENLLPTKATDRENRCQCASQKDKKCW
  NFCQAGKELRAEDIMEKDWNNHKKGKDCSKLGKKCIYQQLVRGRKIRRSSEEHLRQTRSE
  TMRNSVKSSFHDPKLKGKPSRERYVTHNRAHW
• Function: Endothelins are endothelium-derived vasoconstrictor peptides. Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells. Also binds the DEAR/FBXW7-AS1 receptor. Promotes mesenteric arterial wall remodeling via activation of ROCK signaling and subsequent colocalization of NFATC3 with F-actin filaments. NFATC3 then translocates to the nucleus where it subsequently promotes the transcription of the smooth muscle hypertrophy and differentiation marker ACTA2.
• Tissue Specificity: Expressed in lung, placental stem villi vessels and in cultured placental vascular smooth muscle cells.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  HIF-1 sig.ling pathway (hsa04066)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
  TNF sig.ling pathway (hsa04668)
  Melanogenesis (hsa04916)
  Renin secretion (hsa04924)
  Relaxin sig.ling pathway (hsa04926)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Pathways in cancer (hsa05200)
  Hypertrophic cardiomyopathy (hsa05410)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Auriculocondylar syndrome 1	DIS5C8TJ	Strong	Autosomal recessive	[1]
Auriculocondylar syndrome 3	DISSCEJ0	Strong	Autosomal recessive	[1]
Question mark ears, isolated	DISTUCF7	Strong	Autosomal dominant	[1]
Auriculocondylar syndrome	DISW3W1P	Supportive	Autosomal dominant	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Capsaicin	DMGMF6V	Approved	Endothelin-1 (EDN1) decreases the activity of Capsaicin.	[75]
Atenolol	DMNKG1Z	Approved	Endothelin-1 (EDN1) affects the response to substance of Atenolol.	[77]
Irbesartan	DMTP1DC	Investigative	Endothelin-1 (EDN1) affects the response to substance of Irbesartan.	[77]

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Endothelin-1 (EDN1) increases the chemical synthesis of Nitric Oxide.	[76]
D-myo-inositol 1,4,5-trisphosphate	DMNUKIX	Investigative	Endothelin-1 (EDN1) increases the chemical synthesis of D-myo-inositol 1,4,5-trisphosphate.	[79]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Deoxythymidine	DMR90HY	Investigative	Endothelin-1 (EDN1) increases the uptake of Deoxythymidine.	[78]

87 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 Endothelin-1 (EDN1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endothelin-1 (EDN1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Endothelin-1 (EDN1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the activity of Endothelin-1 (EDN1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Endothelin-1 (EDN1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Endothelin-1 (EDN1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Endothelin-1 (EDN1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Endothelin-1 (EDN1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Endothelin-1 (EDN1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Endothelin-1 (EDN1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Endothelin-1 (EDN1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Endothelin-1 (EDN1).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Endothelin-1 (EDN1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Endothelin-1 (EDN1).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Endothelin-1 (EDN1).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Endothelin-1 (EDN1).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Endothelin-1 (EDN1).	[18]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Endothelin-1 (EDN1).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Endothelin-1 (EDN1).	[20]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Endothelin-1 (EDN1).	[21]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Endothelin-1 (EDN1).	[22]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Endothelin-1 (EDN1).	[23]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Endothelin-1 (EDN1).	[24]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Endothelin-1 (EDN1).	[25]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Endothelin-1 (EDN1).	[26]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Endothelin-1 (EDN1).	[27]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Endothelin-1 (EDN1).	[28]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Endothelin-1 (EDN1).	[29]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Endothelin-1 (EDN1).	[30]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Endothelin-1 (EDN1).	[31]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Endothelin-1 (EDN1).	[32]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Endothelin-1 (EDN1).	[34]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Endothelin-1 (EDN1).	[35]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid decreases the expression of Endothelin-1 (EDN1).	[36]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Endothelin-1 (EDN1).	[37]
Bosentan	DMIOGBU	Approved	Bosentan decreases the activity of Endothelin-1 (EDN1).	[38]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the expression of Endothelin-1 (EDN1).	[39]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Endothelin-1 (EDN1).	[40]
Carvedilol	DMHTEAO	Approved	Carvedilol decreases the expression of Endothelin-1 (EDN1).	[41]
Zafirlukast	DMHNQOG	Approved	Zafirlukast decreases the expression of Endothelin-1 (EDN1).	[42]
Amlodipine	DMBDAZV	Approved	Amlodipine affects the expression of Endothelin-1 (EDN1).	[43]
Levamisole	DM5EN79	Approved	Levamisole decreases the expression of Endothelin-1 (EDN1).	[44]
Nisoldipine	DM7ISKJ	Approved	Nisoldipine decreases the expression of Endothelin-1 (EDN1).	[45]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Endothelin-1 (EDN1).	[47]
Glyceryl trinitrate	DMF72W3	Phase 4	Glyceryl trinitrate decreases the expression of Endothelin-1 (EDN1).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Endothelin-1 (EDN1).	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Endothelin-1 (EDN1).	[48]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Endothelin-1 (EDN1).	[4]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Endothelin-1 (EDN1).	[49]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Endothelin-1 (EDN1).	[50]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin decreases the expression of Endothelin-1 (EDN1).	[51]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Endothelin-1 (EDN1).	[52]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of Endothelin-1 (EDN1).	[52]
BQ788	DM6KRLW	Phase 3	BQ788 decreases the activity of Endothelin-1 (EDN1).	[53]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Endothelin-1 (EDN1).	[54]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Endothelin-1 (EDN1).	[21]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Endothelin-1 (EDN1).	[55]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Endothelin-1 (EDN1).	[56]
MK-2206	DMT1OZ6	Phase 2	MK-2206 decreases the expression of Endothelin-1 (EDN1).	[57]
BQ-123	DM0MO8I	Phase 2	BQ-123 decreases the activity of Endothelin-1 (EDN1).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Endothelin-1 (EDN1).	[58]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Endothelin-1 (EDN1).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Endothelin-1 (EDN1).	[60]
Zibotentan	DMIK6C9	Discontinued in Phase 3	Zibotentan decreases the expression of Endothelin-1 (EDN1).	[61]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Endothelin-1 (EDN1).	[11]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Endothelin-1 (EDN1).	[62]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha decreases the expression of Endothelin-1 (EDN1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Endothelin-1 (EDN1).	[63]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Endothelin-1 (EDN1).	[64]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Endothelin-1 (EDN1).	[65]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Endothelin-1 (EDN1).	[8]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Endothelin-1 (EDN1).	[66]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Endothelin-1 (EDN1).	[67]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Endothelin-1 (EDN1).	[68]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Endothelin-1 (EDN1).	[69]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Endothelin-1 (EDN1).	[70]
Chrysin	DM7V2LG	Investigative	Chrysin increases the expression of Endothelin-1 (EDN1).	[62]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Endothelin-1 (EDN1).	[71]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of Endothelin-1 (EDN1).	[67]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Endothelin-1 (EDN1).	[52]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the expression of Endothelin-1 (EDN1).	[67]
Uric acid	DMA1MKT	Investigative	Uric acid increases the expression of Endothelin-1 (EDN1).	[72]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin decreases the expression of Endothelin-1 (EDN1).	[43]
LTC4	DM702WR	Investigative	LTC4 increases the expression of Endothelin-1 (EDN1).	[73]
Tauroursodeoxycholic acid	DMFKRQE	Investigative	Tauroursodeoxycholic acid decreases the expression of Endothelin-1 (EDN1).	[36]
cicaprost	DM7ZJ4H	Investigative	cicaprost decreases the expression of Endothelin-1 (EDN1).	[74]
Green tea	DMQHJTF	Investigative	Green tea increases the expression of Endothelin-1 (EDN1).	[38]

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Zidovudine	DM4KI7O	Approved	Zidovudine increases the secretion of Endothelin-1 (EDN1).	[33]
Lamivudine	DMI347A	Approved	Lamivudine increases the secretion of Endothelin-1 (EDN1).	[33]
Enalaprilat	DMFYAM1	Approved	Enalaprilat decreases the secretion of Endothelin-1 (EDN1).	[46]
Lisinopril	DMUOK4C	Investigative	Lisinopril decreases the secretion of Endothelin-1 (EDN1).	[46]

References

• [1] Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears. Am J Hum Genet. 2013 Dec 5;93(6):1118-25. doi: 10.1016/j.ajhg.2013.10.023. Epub 2013 Nov 21.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] Plasma endothelin-1 as a marker for doxorubicin cardiotoxicity. Int J Cancer. 1995 Sep 4;62(5):542-7. doi: 10.1002/ijc.2910620509.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] BMP-4 expression has prognostic significance in advanced serous ovarian carcinoma and is affected by cisplatin in OVCAR-3 cells. Tumour Biol. 2011 Oct;32(5):985-95. doi: 10.1007/s13277-011-0200-7. Epub 2011 Jun 15.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc Nutr Soc. 2008 Feb;67(1):42-7.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [12] Induction of endothelin-1 expression by oxidative stress in vascular smooth muscle cells. Cardiovasc Pathol. 2001 Nov-Dec;10(6):311-5. doi: 10.1016/s1054-8807(01)00095-3.
• [13] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [19] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [20] The essential role of p53 in hyperpigmentation of the skin via regulation of paracrine melanogenic cytokine receptor signaling. J Biol Chem. 2009 Feb 13;284(7):4343-53. doi: 10.1074/jbc.M805570200. Epub 2008 Dec 18.
• [21] 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.
• [22] Effects of nitroglycerin and dexamethasone on nitric oxide and endothelin derived from alveolar macrophages in patients with mild and middle asthma. Hunan Yi Ke Da Xue Xue Bao. 2000 Aug 28;25(4):363-6.
• [23] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [24] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [25] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [26] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [27] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [28] Evidence of chronic damage to the pulmonary microcirculation in habitual users of alkaloidal ("crack") cocaine. Chest. 2002 Apr;121(4):1231-8. doi: 10.1378/chest.121.4.1231.
• [29] [Effect of simvastatin on endothelin-1 expression in endothelial cell cultured hypoxically]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2008 Jan;39(1):72-5.
• [30] Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
• [31] Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation. Int J Hematol. 2008 Sep;88(2):227-236. doi: 10.1007/s12185-008-0112-5. Epub 2008 Jun 12.
• [32] Cardiac toxicity of high-dose cyclophosphamide in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Int J Hematol. 2007 Jun;85(5):408-14. doi: 10.1532/IJH97.E0620.
• [33] Nucleoside reverse transcriptase inhibitors induce a mitophagy-associated endothelial cytotoxicity that is reversed by coenzyme Q10 cotreatment. Toxicol Sci. 2013 Aug;134(2):323-34. doi: 10.1093/toxsci/kft105. Epub 2013 May 2.
• [34] Role of endothelin-1 in the development of a special type of cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:272S-275S. doi: 10.1042/CS103S272S.
• [35] Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U-2 OS cells. Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
• [36] Ursodeoxycholic acid inhibits endothelin-1 production in human vascular endothelial cells. Eur J Pharmacol. 2004 Nov 28;505(1-3):67-74. doi: 10.1016/j.ejphar.2004.10.042.
• [37] 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.
• [38] ?-adrenoceptors and muscarinic receptors mediate opposing effects on endothelin-1 expression in human lung fibroblasts. Eur J Pharmacol. 2012 Sep 15;691(1-3):218-24. doi: 10.1016/j.ejphar.2012.07.002. Epub 2012 Jul 13.
• [39] Bezafibrate reduces heart rate and blood pressure in patients with hypertriglyceridemia. J Hypertens. 2001 Apr;19(4):749-55. doi: 10.1097/00004872-200104000-00012.
• [40] Effect of heparin on endothelin-1 production by cultured human endothelial cells. J Cardiovasc Pharmacol. 1993;22 Suppl 8:S46-8. doi: 10.1097/00005344-199322008-00014.
• [41] Carvedilol inhibits endothelin-1 biosynthesis in cultured human coronary artery endothelial cells. J Mol Cell Cardiol. 1998 Jan;30(1):167-73. doi: 10.1006/jmcc.1997.0582.
• [42] Effects of leukotriene receptor antagonist on chronic obstructive [correction of obstractive] pulmonary disease induced pulmonary hypertension. Chin Med J (Engl). 2003 Mar;116(3):459-61.
• [43] Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy. Nephrol Dial Transplant. 2001;16 Suppl 1:114-6. doi: 10.1093/ndt/16.suppl_1.114.
• [44] Levamisole induced apoptosis in cultured vascular endothelial cells. Br J Pharmacol. 2000 Dec;131(8):1577-83.
• [45] Plasma endothelin-1 concentrations in patients with coronary artery disease during stress test before and after nisoldipine administration. Acta Cardiol. 1996;51(2):165-72.
• [46] Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: evidence of an oxidant-sensitive pathway. Mediators Inflamm. 2008;2008:305087. doi: 10.1155/2008/305087. Epub 2008 Dec 1.
• [47] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [48] Inhibition of cyclic strain-induced endothelin-1 gene expression by resveratrol. Hypertension. 2003 Dec;42(6):1198-205. doi: 10.1161/01.HYP.0000103162.76220.51. Epub 2003 Nov 17.
• [49] Physiological concentrations of dietary polyphenols regulate vascular endothelial cell expression of genes important in cardiovascular health. Br J Nutr. 2010 May;103(10):1398-403.
• [50] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [51] The effects of atorvastatin (10 mg) on systemic inflammation in heart failure. Am J Cardiol. 2005 Dec 15;96(12):1699-704. doi: 10.1016/j.amjcard.2005.07.092. Epub 2005 Oct 28.
• [52] Mapping the dynamics of Nrf2 antioxidant and NFB inflammatory responses by soft electrophilic chemicals in human liver cells defines the transition from adaptive to adverse responses. Toxicol In Vitro. 2022 Oct;84:105419. doi: 10.1016/j.tiv.2022.105419. Epub 2022 Jun 17.
• [53] Actions of endothelin and corticotropin releasing factor in the guinea-pig ileum: no evidence for an interaction with capsaicin-sensitive neurons. Neuropeptides. 2003 Aug;37(4):220-32. doi: 10.1016/s0143-4179(03)00048-9.
• [54] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [55] Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
• [56] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [57] Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBP axis and inducing M1 macrophage polarization. Cell Biol Toxicol. 2022 Aug;38(4):611-628. doi: 10.1007/s10565-021-09636-7. Epub 2021 Aug 16.
• [58] 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.
• [59] 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.
• [60] 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. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [61] ETAR antagonist ZD4054 exhibits additive effects with aromatase inhibitors and fulvestrant in breast cancer therapy, and improves in vivo efficacy of anastrozole. Breast Cancer Res Treat. 2010 Sep;123(2):345-57. doi: 10.1007/s10549-009-0644-2. Epub 2009 Nov 27.
• [62] A p38-p65 transcription complex induced by endothelin-1 mediates signal transduction in cancer cells. Biochim Biophys Acta. 2008 Sep;1783(9):1613-22.
• [63] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [64] 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.
• [65] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [66] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [67] High-fat feeding reduces endothelium-dependent vasodilation in rats: differential mechanisms for saturated and unsaturated fatty acids? Clin Exp Pharmacol Physiol. 2006 Aug;33(8):708-13.
• [68] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [69] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [70] Mitochondrial ROS-K+ channel signaling pathway regulated secretion of human pulmonary artery endothelial cells. Free Radic Res. 2012 Dec;46(12):1437-45. doi: 10.3109/10715762.2012.724532. Epub 2012 Sep 27.
• [71] Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors. Toxicology. 2010 Jan 31;268(1-2):19-24. doi: 10.1016/j.tox.2009.11.013. Epub 2009 Nov 14.
• [72] Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells. Braz J Med Biol Res. 2015 Jan;48(1):51-56. doi: 10.1590/1414-431x20144032. Epub 2014 Oct 24.
• [73] [Zafirlukast inhibition of leukotriene C4 induced endothelin-1 expression in human airway structural cell]. Zhonghua Jie He He Hu Xi Za Zhi. 2000 Oct;23(10):617-20.
• [74] Cyclooxygenase-2 acts as an endogenous brake on endothelin-1 release by human pulmonary artery smooth muscle cells: implications for pulmonary hypertension. Mol Pharmacol. 2002 Nov;62(5):1147-53. doi: 10.1124/mol.62.5.1147.
• [75] Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas deferens. Eur J Pharmacol. 1999 Jan 8;364(2-3):183-91. doi: 10.1016/s0014-2999(98)00841-3.
• [76] The neurogenic vasodilator response to endothelin-1: a study in human skin in vivo. Exp Physiol. 2000 Nov;85(6):839-46.
• [77] Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 May;27(5):287-90. doi: 10.1002/clc.4960270510.
• [78] Role of endothelin in the human craniofacial morphogenesis. J Craniofac Genet Dev Biol. 1998 Oct-Dec;18(4):183-94.
• [79] Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11 proteins and associated signaling in vascular smooth muscle cells. Free Radic Biol Med. 2010 Nov 15;49(9):1395-405. doi: 10.1016/j.freeradbiomed.2010.07.023. Epub 2010 Aug 5.