Details of the Drug Combination

General Information of Drug Combination (ID: DCPPMDU)

Drug Combination Name

Mecamylamine Everolimus

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Mecamylamine DMGQFYB

Everolimus DM8X2EH

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: KBM-7

Zero Interaction Potency (ZIP) Score: 1.89

Bliss Independence Score: 1.89

Loewe Additivity Score: 7.83

LHighest Single Agent (HSA) Score: 7.85

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Mecamylamine

Disease Entry	ICD 11	Status	REF
Essential hypertension	BA00	Approved	[2]

Mecamylamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nicotinic acetylcholine receptor (nAChR)	TTJSZTB	NOUNIPROTAC	Antagonist	[7]
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Mecamylamine Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Expression	[6]
Receptor-type tyrosine-protein phosphatase alpha (PTPRA)	OTZA82J1	PTPRA_HUMAN	Decreases Expression	[6]
Contactin-1 (CNTN1)	OT7RNPEY	CNTN1_HUMAN	Increases Expression	[6]
Fasciculation and elongation protein zeta-1 (FEZ1)	OTWCXPRE	FEZ1_HUMAN	Decreases Expression	[6]
Lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF)	OTT5JX1F	LITAF_HUMAN	Decreases Expression	[6]
Echinoderm microtubule-associated protein-like 4 (EML4)	OTJC45TA	EMAL4_HUMAN	Decreases Expression	[6]
Stress-induced-phosphoprotein 1 (STIP1)	OT7TXLOX	STIP1_HUMAN	Decreases Expression	[8]
Golgin subfamily A member 4 (GOLGA4)	OTCMEHNJ	GOGA4_HUMAN	Increases Expression	[8]
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⏷ Show the Full List of 8 DOT(s)

Indication(s) of Everolimus

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[3]
Advanced/metastatic breast cancer	2C60	Approved	[2]
Brainstem neoplasm	N.A.	Approved	[3]
Breast carcinoma	N.A.	Approved	[3]
Graft-versus-host disease	4B24	Approved	[3]
Intracranial meningioma	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]
Lung cancer	2C25.0	Approved	[3]
Mucosal melanoma	N.A.	Approved	[3]
Multiple sclerosis	8A40	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Prostate cancer	2C82.0	Approved	[3]
Renal cell carcinoma	2C90	Approved	[4]
Salivary gland squamous cell carcinoma	N.A.	Approved	[3]
Tuberous sclerosis	LD2D.2	Approved	[3]
Kidney cancer	2C90.0	Phase 3	[4]
Castration-resistant prostate carcinoma	N.A.	Investigative	[3]
Colon cancer	2B90.Z	Investigative	[3]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[5]
Neuroblastoma	2D11.2	Investigative	[3]
Pancreatic acinar cell carcinoma	N.A.	Investigative	[3]
Polycystic kidney disease	GB8Y	Investigative	[3]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[5]

Everolimus Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[9]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[5]
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Everolimus Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
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Everolimus Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
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References

1	Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	Everolimus FDA Label
4	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: 5889).
5	Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6	Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem. 2003 May 2;278(18):15633-40.
7	Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens. 2002 Jul;16(7):453-7.
8	Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
9	Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
10	Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
11	The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.