Details of the Drug Combination

General Information of Drug Combination (ID: DCMM90O)

• Drug Combination Name: Tamsulosin + Finasteride
• Indication: Benign Prostatic Hyperplasia; Status: Phase 1 [1]
• Component Drugs:
  Tamsulosin (DM5QF9V): Small molecular drug
  Finasteride (DMWV3TZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tamsulosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[2]
Urinary retention	MF50.3	Approved	[3]

Tamsulosin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Modulator	[6]

Tamsulosin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

Tamsulosin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Affects Binding	[8]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[9]

Indication(s) of Finasteride

Disease Entry	ICD 11	Status	REF
Baldness, male pattern	N.A.	Approved	[4]
Benign prostatic hyperplasia	GA90	Approved	[5]
Retinopathy	9B71	Approved	[4]

Finasteride Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Oxo-5-alpha-steroid 4-dehydrogenase (SRD5A)	TT2A0DR	S5A1_HUMAN; S5A2_HUMAN; PORED_HUMAN	Inhibitor	[10]
Steroid 5-alpha-reductase 2 (SRD5A2)	TTT02K8	S5A2_HUMAN	Inhibitor	[11]

Finasteride Interacts with 3 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	[13]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[13]

Finasteride Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1)	OTQRET2B	S5A1_HUMAN	Decreases Activity	[14]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[15]
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)	OTTG0NFD	S5A2_HUMAN	Decreases Activity	[16]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[17]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Response To Substance	[19]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Benign Prostate Hyperplasia	DCRY36V	N. A.	Phase 1	[20]

References

• [1] ClinicalTrials.gov (NCT01534351) Comparison of Finasteride and Tamsulosin for Treatment of Benign Prostatic Hyperplasia (BPH) (MK-0906A-149 AM2)
• [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: 488).
• [3] Tamsulosin FDA Label
• [4] Finasteride FDA Label
• [5] 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: 6818).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes. Xenobiotica. 1998 Oct;28(10):909-22.
• [8] Cell membrane chromatography competitive binding analysis for characterization of 1A adrenoreceptor binding interactions. Anal Bioanal Chem. 2011 Jul;400(10):3625-33. doi: 10.1007/s00216-011-5026-z. Epub 2011 May 5.
• [9] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [10] The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [13] Drug Interactions Flockhart Table
• [14] Inhibition of the activity of 'basic' 5 alpha-reductase (type 1) detected in DU 145 cells and expressed in insect cells. J Steroid Biochem Mol Biol. 1994 Mar;48(4):347-52.
• [15] Antiandrogenic effects of novel androgen synthesis inhibitors on hormone-dependent prostate cancer. Cancer Res. 2000 Dec 1;60(23):6630-40.
• [16] Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells. Toxicol In Vitro. 2007 Apr;21(3):502-8.
• [17] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [18] Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
• [19] Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone. J Neurosci. 2009 May 20;29(20):6449-60. doi: 10.1523/JNEUROSCI.0708-09.2009.
• [20] ClinicalTrials.gov (NCT01736033) Advanced Benefits of Alpha-blocker Monotherapy on Lower Urinary Tracts Symptoms(LUTS) Patients