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

General Information of Drug (ID: DM8TUPF)

• Drug Name: Milrinone Drug Info
• Synonyms: Corotrop; Corotrope; Milrila; Milrinona; Milrinonum; Primacor; Milrinona [Spanish]; Milrinonum [Latin]; M 4659; M1663; YM 018; MILRINONE LACTATE IN DEXTROSE 5% IN PLASTIC CONTAINER; Milrila (TN); PRIMACOR IN DEXTROSE 5% IN PLASTIC CONTAINER; Primacor (TN); WIN 47203-2; Win-47203; Milrinone [USAN:BAN:INN]; Win-47203-2; Milrinone (JAN/USAN/INN); 1,6-Dihydro-2-methyl-6-oxo(3,4'-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-(3,4'-bipyridine)-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile; 1,6-Dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile; 111GE027; 2-methyl-6-oxo-1,6-dihydro-3,4'-bipyridine-5-carbonitrile; 3-Cyano-6-methyl-5-(4-pyridyl)-2-pyridone; 6-Methyl-5-(4-pyridyl)-2-pyridone-3-carbonitrile; 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile

Indication

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[1]
Cardiomyopathy	BC43	Investigative	[2]

• Therapeutic Class: Cardiotonic Agents
• Cross-matching ID:
  PubChem CID: 4197
  ChEBI ID: CHEBI:50693
  CAS Number: CAS 78415-72-2
  TTD Drug ID: DM8TUPF

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 3 (PDE3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[3]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[3]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[6]
Enoximone	DMQVZJD	Congestive heart failure	BD10	Approved	[7]
Olprinone	DMWBQKU	Heart failure	BD10-BD13	Approved	[8]
Inamrinone Lactate	DMRMFP4	Cardiac disease	BA00-BE2Z	Approved	[9]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[10]
Tipelukast	DMS9BDQ	Asthma	CA23	Phase 2	[11]
RPL-554	DMLD4VQ	Allergic rhinitis	CA08.0	Phase 2	[12]
Org-30029	DMDZ4R2	Heart failure	BD10-BD13	Phase 2	[13]

Drug(s) Affected By C-reactive protein (CRP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lidocaine	DML4ZOT	Anaesthesia	9A78.6	Approved	[14]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[15]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[16]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[18]
Acalabrutinib	DM7GCVW	leukaemia	2A60-2B33	Approved	[19]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[20]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[21]
Tibolone	DM78XFG	Anabolic metabolism	5C50-5C8Z	Approved	[22]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[23]

Drug(s) Affected By Cystic fibrosis transmembrane conductance regulator (CFTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ivacaftor	DMZC1HS	Cystic fibrosis	CA25	Approved	[24]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[25]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[5]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]
Miglustat	DM5J64S	Niemann-Pick disease type C		Approved	[27]
Glibenclamide	DM8JXPZ	Diabetic complication	5A2Y	Approved	[28]
Oxidized glutathione	DM9EQC0	Breast cancer	2C60-2C65	Approved	[29]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[29]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[30]
Flufenamic Acid	DMC8VNH	Dysmenorrhea	GA34.3	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 3 (PDE3)	TTZCG4L	NOUNIPROTAC	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Gene/Protein Processing	[4]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Gene/Protein Processing	[5]

References

• [1] 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: 5225).
• [2] Milrinone FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting. Anesth Analg. 2002 Jan;94(1):22-30, table of contents. doi: 10.1097/00000539-200201000-00005.
• [5] Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells. Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):410-8. doi: 10.1165/rcmb.2002-0247OC. Epub 2003 Apr 24.
• [6] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [7] In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology. 2003 Apr;98(4):944-9.
• [8] Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev. 2002 Fall;20(3):163-74.
• [9] Effects of amrinone on hepatic ischemia-reperfusion injury in rats. J Hepatol. 2002 Jul;37(1):31-8.
• [10] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [11] Company report (MediciNova)
• [12] Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials.Lancet Respir Med.2013 Nov;1(9):714-27.
• [13] Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium. Circ Res. 1993 Mar;72(3):597-606.
• [14] 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.
• [15] C-Reactive protein levels over time and cardiovascular risk in HIV-infected individuals suppressed on an indinavir-based regimen: AIDS Clinical Trials Group 5056s. AIDS. 2004 Dec 3;18(18):2434-7.
• [16] Simvastatin combined with ramipril treatment in hypercholesterolemic patients. Hypertension. 2004 Aug;44(2):180-5. doi: 10.1161/01.HYP.0000133310.42762.25. Epub 2004 Jun 7.
• [17] The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur J Pharmacol. 2007 Feb 28;557(2-3):221-9.
• [18] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [19] Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol. 2020 Jun 5;5(48):eabd0110. doi: 10.1126/sciimmunol.abd0110. Epub 2020 Jun 5.
• [20] The influence of alclofenac treatment on acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in patients with rheumatoid arthritis. Curr Med Res Opin. 1975;3(5):286-97. doi: 10.1185/03007997509114779.
• [21] Intractable insomnia after cessation of treatment with thalidomide. Gastroenterology. 2001 May;120(6):1567-8. doi: 10.1053/gast.2001.24495.
• [22] Effects of hormone treatment on hemostasis variables. Climacteric. 2007 Oct;10 Suppl 2:32-7. doi: 10.1080/13697130701598548.
• [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] Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825.
• [25] 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.
• [26] Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoids. Am J Respir Cell Mol Biol. 2004 Sep;31(3):351-7. doi: 10.1165/rcmb.2002-0086OC. Epub 2004 Jun 10.
• [27] Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutation of glycine 622. J Pharmacol Exp Ther. 2008 Apr;325(1):89-99. doi: 10.1124/jpet.107.134502. Epub 2008 Jan 29.
• [28] Comparative pharmacology of the activity of wild-type and G551D mutated CFTR chloride channel: effect of the benzimidazolone derivative NS004. J Membr Biol. 2003 Jul 15;194(2):109-17. doi: 10.1007/s00232-003-2030-z.
• [29] Reversible silencing of CFTR chloride channels by glutathionylation. J Gen Physiol. 2005 Feb;125(2):127-41. doi: 10.1085/jgp.200409115. Epub 2005 Jan 18.
• [30] 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.
• [31] Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J Gen Physiol. 2004 Aug;124(2):125-37. doi: 10.1085/jgp.200409059.