Details of the Drug Combination

General Information of Drug Combination (ID: DCVY7EQ)

Drug Combination Name

Brinzolamide Brimonidine

Indication

Disease Entry	Status	REF
Open-Angle Glaucoma	Phase 3	[1]

Component Drugs

Brinzolamide DMBAPFG

Brimonidine DMQLT4N

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Brinzolamide

Disease Entry	ICD 11	Status	REF
Ocular hypertension	9C61.01	Approved	[2]
Open-angle glaucoma	9C61	Approved	[3]

Brinzolamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Carbonic anhydrase IV (CA-IV)	TTZHA0O	CAH4_HUMAN	Modulator	[6]
------------------------------------------------------------------------------------

Brinzolamide Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
------------------------------------------------------------------------------------

Brinzolamide Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[8]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Affects Expression	[8]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[8]
------------------------------------------------------------------------------------

Indication(s) of Brimonidine

Disease Entry	ICD 11	Status	REF
Ocular hypertension	9C61.01	Approved	[4]
Glaucoma/ocular hypertension	9C61	Phase 3	[5]

Brimonidine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor alpha-2C (ADRA2C)	TT2NUT5	ADA2C_HUMAN	Modulator	[4]
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[9]
------------------------------------------------------------------------------------

Brimonidine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases ADR	[10]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Glaucoma	DCES7YX	N. A.	Phase 1	[11]
------------------------------------------------------------------------------------

References

1	ClinicalTrials.gov (NCT02339584) Efficacy and Safety of Brinzolamide/Brimonidine Fixed Combination BID Compared to Brinzolamide BID Plus Brimonidine BID in Subjects With Open-Angle Glaucoma (OAG) or Ocular Hypertension (OHT)
2	Brinzolamide 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: 6797).
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: 520).
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
8	Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
9	Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum. 2000 Aug;43(8):1886-90.
10	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.
11	ClinicalTrials.gov (NCT00800540) Circadian Ocular Perfusion Pressure and Ocular Blood Flow