Details of the Drug Combination

General Information of Drug Combination (ID: DCE29MG)

• Drug Combination Name: Minoxidil + Finasteride
• Indication: Androgenetic Alopecia; Status: Phase 2 [1]
• Component Drugs:
  Minoxidil (DMA2Z4F): Small molecular drug
  Finasteride (DMWV3TZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Minoxidil

Disease Entry	ICD 11	Status	REF
Alopecia	ED70	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Malignant essential hypertension	BA00	Approved	[2]

Minoxidil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Modulator	[6]

Minoxidil Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[8]

Minoxidil Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Sulfotransferase 1A1 (SULT1A1)	OT0K7JIE	ST1A1_HUMAN	Increases Sulfation	[9]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Decreases Expression	[10]
Renin (REN)	OT52GZR2	RENI_HUMAN	Affects Expression	[11]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[10]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Decreases Expression	[10]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Decreases Expression	[10]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[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	[12]
Steroid 5-alpha-reductase 2 (SRD5A2)	TTT02K8	S5A2_HUMAN	Inhibitor	[13]

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	[14]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[15]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[15]

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	[16]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[17]
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)	OTTG0NFD	S5A2_HUMAN	Decreases Activity	[18]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[19]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[20]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Response To Substance	[21]

References

• [1] ClinicalTrials.gov (NCT05990400) Effectiveness and Safety of Topical Finasteride and Minoxidil Combination Compared to Topical Minoxidil for The Treatment of Male Androgenetic Alopecia
• [2] Minoxidil FDA Label
• [3] 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: 4254).
• [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] Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid. Drug Metab Dispos. 2004 Apr;32(4):413-23.
• [8] Sulfation of minoxidil by multiple human cytosolic sulfotransferases. Chem Biol Interact. 1998 Feb 20;109(1-3):53-67.
• [9] Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms. Drug Metab Dispos. 2001 Mar;29(3):274-81.
• [10] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [11] Need for beta-blockade in hypertension reduced with long-term minoxidil. Br Med J. 1978 Aug 5;2(6134):385-8. doi: 10.1136/bmj.2.6134.385.
• [12] 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.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [15] Drug Interactions Flockhart Table
• [16] 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.
• [17] Antiandrogenic effects of novel androgen synthesis inhibitors on hormone-dependent prostate cancer. Cancer Res. 2000 Dec 1;60(23):6630-40.
• [18] Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells. Toxicol In Vitro. 2007 Apr;21(3):502-8.
• [19] 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.
• [20] 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.
• [21] 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.