Details of the Drug Combination

General Information of Drug Combination (ID: DC72YFX)

• Drug Combination Name: Brinzolamide + Latanoprost
• Indication: Ocular Hypertension; Status: Phase 4 [1]
• Component Drugs:
  Brinzolamide (DMBAPFG): Small molecular drug
  Latanoprost (DMI5OXG): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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	[8]

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	[9]

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	[10]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Affects Expression	[10]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[10]

Indication(s) of Latanoprost

Disease Entry	ICD 11	Status	REF
Ocular hypertension	9C61.01	Approved	[4]
Open-angle glaucoma	9C61	Approved	[5]
OPTN-related open angle glaucoma	N.A.	Approved	[4]
Glaucoma/ocular hypertension	9C61	Phase 2	[6]
Ocular disease	1F00.1Z	Investigative	[7]

Latanoprost Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin F2-alpha receptor (PTGFR)	TTT2ZAR	PF2R_HUMAN	Agonist	[11]

Latanoprost Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[12]
Organic anion transporting polypeptide 2A1 (SLCO2A1)	DT021JD	SO2A1_HUMAN	Substrate	[12]

Latanoprost Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[13]

References

• [1] ClinicalTrials.gov (NCT01937312) Effect of SIMBRINZA Suspension as an Added Therapy to a Prostaglandin Analogue
• [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] Latanoprost 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: 1961).
• [6] Clinical pipeline report, company report or official report of Mati therapeutics.
• [7] 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: 344).
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [10] 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.
• [11] PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia. Neurotox Res. 2009 Jan;15(1):62-70.
• [12] The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11.
• [13] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.