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

General Information of Drug (ID: DMTWLXY)

• Drug Name: Entresto Drug Info
• Synonyms: Sacubitril valsartan sodium hydrate; UNII-WB8FT61183; Sacubitril mixture with valsartan; WB8FT61183; Entresto (TN); Valsartan mixture with AHU-377; MolPort-042-624-138; C96H120N12Na6O21; 9052AF; AKOS026670199; ACN-036829; 3-(1-Biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-3'-methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylmethyl)amino)butyrate; AK198922; AC-29037; Sacubitril valsartan sodium hydrate (JAN); FT-0700025; D10226; L-Valine, N-(1-oxopentyl)-N-((2'-(2H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl)-, compd. wi

Indication

Disease Entry	ICD 11	Status	REF
Acute myocardial infarction	BA41	Phase 3	[1]
Heart failure	BD10-BD13	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 71449007
  CAS Number: CAS 936623-90-4
  TTD Drug ID: DMTWLXY
  INTEDE Drug ID: DR1876

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[4]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[5]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[6]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[7]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[8]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[9]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[10]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[11]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[5]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[12]

Drug(s) Affected By Angiotensinogen (AGT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Reboxetine	DM26PRD	Depression	6A70-6A7Z	Approved	[16]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[17]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[18]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[19]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[20]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[21]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Gene/Protein Processing	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] FDA label of Sacubitril and valsartan. The 2020 official website of the U.S. Food and Drug Administration.
• [3] Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14. doi: 10.1177/0091270009343932. Epub 2009 Nov 23.
• [4] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [5] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [6] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [7] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [8] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [9] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [10] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [11] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [12] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [13] Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect. 2015 Jan;123(1):80-7. doi: 10.1289/ehp.1408437. Epub 2014 Aug 19.
• [14] Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids. Toxicology. 2017 Apr 15;381:51-63.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans. Hypertension. 2006 Jul;48(1):120-6. doi: 10.1161/01.HYP.0000225424.13138.5d. Epub 2006 May 22.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.