Details of the Drug Combination

General Information of Drug Combination (ID: DCQG3VC)

• Drug Combination Name: Selegiline + Tadalafil
• Indication: Parkinson's Disease; Status: Phase 4 [1]
• Component Drugs:
  Selegiline (DM6034S): Small molecular drug
  Tadalafil (DMJZHT1): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Selegiline

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[2]
Skin imperfections	EK71	Patented	[3]
Chemotherapy-induced nausea	MD90	Discontinued in Phase 3	[4]

Selegiline Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Antagonist	[8]
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Inhibitor	[3]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[9]

Selegiline Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Phosphorylation	[7]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[7]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[7]

Indication(s) of Tadalafil

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[5]
Erectile dysfunction	HA01.1	Approved	[6]
Plasma cell myeloma	2A83.1	Approved	[5]
Pulmonary hypertension	BB01	Approved	[5]
Priapism	N.A.	Investigative	[5]

Tadalafil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Inhibitor	[10]

Tadalafil Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Tadalafil Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]

References

• [1] ClinicalTrials.gov (NCT02225548) Sagene 2014 - Parkinson's Disease and Erectile Dysfunction
• [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: 6639).
• [3] Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [5] Tadalafil FDA Label
• [6] 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: 7299).
• [7] Role of the redox protein thioredoxin in cytoprotective mechanism evoked by (-)-deprenyl. Mol Pharmacol. 2005 Nov;68(5):1408-14. doi: 10.1124/mol.105.012302. Epub 2005 Aug 12.
• [8] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [9] 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. (Target id: 2490).
• [10] Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
• [11] In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil. Biol Pharm Bull. 2017;40(8):1314-1319.
• [12] Contribution of CYP3A isoforms to dealkylation of PDE5 inhibitors: a comparison between sildenafil N-demethylation and tadalafil demethylenation. Biol Pharm Bull. 2015;38(1):58-65.