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

General Information of Drug (ID: DM471ZH)

• Drug Name: ORE-1001 Drug Info
• Synonyms: MLN-4760; UNII-4LD0ZHV25K; 4LD0ZHV25K; CHEMBL429844; MLN 4760; 305335-31-3; (S,S)-2-{1-CARBOXY-2-[3-(3,5-DICHLORO-BENZYL)-3H-IMIDAZOL-4-YL]-ETHYLAMINO}-4-METHYL-PENTANOIC ACID; XX5; N-[(1s)-1-carboxy-3-methylbutyl]-3-(3,5-dichlorobenzyl)-l-histidine; (2S)-2-[[(2S)-3-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]-1-hydroxy-1-oxopropan-2-yl]amino]-4-methylpentanoic acid; AC1L9LSK; GTPL7866; SCHEMBL1691048; BDBM21489; DTXSID70184609; ZINC1549629; DB12271; HY-19414; CS-0015513

Indication

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Phase 1/2	[1]
Type-2 diabetes	5A11	Discontinued in Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 448281
  ChEBI ID: CHEBI:166834
  CAS Number: CAS 305335-31-3
  TTD Drug ID: DM471ZH

Molecule-Related Drug Atlas

Drug(s) Targeting Angiotensin-converting enzyme 2 (ACE2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK2586881	DMU5EVR	Acute lung injury	NB32.3	Phase 2	[6]
XNT	DMPOGXU	Discovery agent	N.A.	Investigative	[7]
PMID18324760C28	DMCTFWE	Discovery agent	N.A.	Investigative	[8]
Captopril	DM458UM	Chronic heart failure	BD1Z	Approved	[27]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[28]
Dantrolene	DM1D8XY	Hyperthermia	MG26	Approved	[28]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[28]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[28]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[28]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[28]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[28]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[28]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[28]

Drug(s) Affected By Angiotensinogen (AGT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[9]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[10]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[11]
Reboxetine	DM26PRD	Depression	6A70-6A7Z	Approved	[12]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[13]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[17]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[18]

Drug(s) Affected By Angiotensin-converting enzyme (ACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[19]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[19]
Quinapril	DMR8H31	Chronic heart failure	BD1Z	Approved	[19]
Cilazapril	DM4V6JA	Congestive heart failure	BD10	Approved	[20]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[21]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[22]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[25]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin-converting enzyme 2 (ACE2)	TTUI5H7	ACE2_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Gene/Protein Processing	[4]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Gene/Protein Processing	[4]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Biochemical Pathways	[5]

References

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• [2] 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: 7866).
• [3] Effects of the ACE2 inhibitor GL1001 on acute dextran sodium sulfate-induced colitis in mice. Inflamm Res. 2009 Nov;58(11):819-27.
• [4] Angiotensin converting enzyme versus angiotensin converting enzyme-2 selectivity of MLN-4760 and DX600 in human and murine bone marrow-derived cells. Eur J Pharmacol. 2016 Mar 5;774:25-33. doi: 10.1016/j.ejphar.2016.01.007. Epub 2016 Feb 3.
• [5] Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney. Sci Rep. 2016 Sep 21;6:33678. doi: 10.1038/srep33678.
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• [13] Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther. 1980 Apr;27(4):533-43. doi: 10.1038/clpt.1980.75.
• [14] Simvastatin treatment in subjects at high cardiovascular risk modulates AT1R expression on circulating monocytes and T lymphocytes. J Hypertens. 2008 Jun;26(6):1147-55. doi: 10.1097/HJH.0b013e3282f97dde.
• [15] Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites. Am J Physiol Renal Physiol. 2005 May;288(5):F1044-52. doi: 10.1152/ajprenal.00142.2004. Epub 2004 Dec 21.
• [16] 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.
• [17] Effects of lisinopril on cardiorespiratory, neuroendocrine, and renal function in patients with asymptomatic left ventricular dysfunction. Br Heart J. 1993 Jun;69(6):512-5. doi: 10.1136/hrt.69.6.512.
• [18] Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists. Hypertension. 1999 Mar;33(3):850-5. doi: 10.1161/01.hyp.33.3.850.
• [19] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [20] [A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):581-4.
• [21] ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrol Dial Transplant. 2000 Oct;15(10):1617-23. doi: 10.1093/ndt/15.10.1617.
• [22] Targeted catalytic inactivation of angiotensin converting enzyme by lisinopril-coupled transition-metal chelates. J Am Chem Soc. 2012 Feb 22;134(7):3396-410. doi: 10.1021/ja208791f. Epub 2012 Feb 10.
• [23] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [24] 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.
• [25] "Crack" cocaine-induced syndrome mimicking sarcoidosis. Am J Med Sci. 1999 Jun;317(6):416-8. doi: 10.1097/00000441-199906000-00011.
• [26] Nicotine induced changes in gene expression by human coronary artery endothelial cells. Atherosclerosis. 2001 Feb 1;154(2):277-83.
• [27] Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women. Clin Pharmacol Ther. 2007 Aug;82(2):187-96. doi: 10.1038/sj.clpt.6100214. Epub 2007 May 2.
• [28] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.