Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM6KRLW)

• Drug Name: BQ788 Drug Info
• Synonyms: (2R)-2-[[(2R)-2-amino-3-(1-methoxycarbonylindol-3-yl)propanoyl]-[(2S)-2-[[(2R,6S)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]hexanoic acid; BQ 788; AC1MIWQ3; GTPL1010; SCHEMBL18429752

Indication

Disease Entry	ICD 11	Status	REF
Acute kidney injury	GB60	Phase 3	[1]
Encephalopathy	8E47	Phase 3	[2]
Myasthenia gravis	8C6Y	Phase 3	[2]
Neuromyelitis optica	8A43	Phase 3	[1]
Hypertension	BA00-BA04	Phase 1	[3]

• Cross-matching ID:
  PubChem CID: 16759603
  CAS Number: CAS 156161-89-6
  TTD Drug ID: DM6KRLW

Molecule-Related Drug Atlas

Drug(s) Targeting Endothelin B receptor (EDNRB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[7]
Macitentan	DMP79A1	Cardiovascular disease	BA00-BE2Z	Approved	[8]
PD-145065	DMWVBTQ	Hypertension	BA00-BA04	Phase 2	[9]
SPI-1620	DMNPRMC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
ENB003	DMK2B3S	Melanoma	2C30	Phase 1/2	[11]
J-104132	DM5E6MK	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[12]
ENRASENTAN	DM05F1Z	Pulmonary arterial hypertension	BB01.0	Discontinued in Phase 2	[13]
SB-209670	DMJYW80	Arrhythmia	BC9Z	Discontinued in Phase 2	[14]
ET-1	DMA85ND	N. A.	N. A.	Phase 0	[15]
PD142893	DMFA27N	N. A.	N. A.	Terminated	[16]

Drug(s) Affected By Endothelin-1 (EDN1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[20]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[21]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[22]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[23]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[24]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[25]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[26]

Drug(s) Affected By Coxsackievirus and adenovirus receptor (CXADR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[27]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[28]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[31]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[5]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[32]
Valsartan	DMREUQ6	Chronic heart failure	BD1Z	Approved	[5]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[33]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Endothelin B receptor (EDNRB)	TT3ZTGU	EDNRB_HUMAN	Antagonist	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Coxsackievirus and adenovirus receptor (CXADR)	OT9ZP02A	CXAR_HUMAN	Gene/Protein Processing	[5]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Gene/Protein Processing	[6]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] URL: http://www.guidetopharmacology.org 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. (Ligand id: 1010).
• [4] BQ788, an endothelin ET(B) receptor antagonist, attenuates stab wound injury-induced reactive astrocytes in rat brain. Glia. 1999 May;26(3):268-71.
• [5] Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. J Gen Virol. 2010 Aug;91(Pt 8):1959-1970. doi: 10.1099/vir.0.020065-0. Epub 2010 Apr 14.
• [6] 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.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [9] Reversal of established responses to endothelin-1 in vivo and in vitro by the endothelin receptor antagonists, BQ-123 and PD 145065. Br J Pharmacol. 1994 May;112(1):207-13.
• [10] Clinical pipeline report, company report or official report of Spectrum Phamaceuticals (2009).
• [11] ClinicalTrials.gov (NCT04205227) A Phase 1/2A Trial of ENB 003 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors. U.S.National Institutes of Health.
• [12] Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist. J Pharmacol Exp Ther. 1999 Jun;289(3):1262-70.
• [13] Enrasentan, an antagonist of endothelin receptors. Cardiovasc Drug Rev. 2003 Spring;21(1):1-16.
• [14] Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat. Br J Pharmacol. 1996 May;118(1):198-204.
• [15] IRL 2500: A potent ETB selective endothelin antagonist, Bioorg. Med. Chem. Lett. 6(19):2323-2328 (1996).
• [16] Human optic nerve head astrocytes as a target for endothelin-1. Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2704-13.
• [17] ?-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.
• [18] 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.
• [19] 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.
• [20] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [21] [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.
• [22] Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc Nutr Soc. 2008 Feb;67(1):42-7.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [28] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [29] 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.
• [30] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [31] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [32] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [33] 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. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [34] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.