Details of the Drug

General Information of Drug (ID: DMBAPFG)

Drug Name

Brinzolamide

Synonyms

Azopt; Birnzolamide; Alcon brand of brinzolamide; Allphar brand of brinzolamide; Brinzolamide [USAN]; AL 4862; AL04862; BZ1; AL-4862; Azopt (TN); Brinzolamide (BRZ); Brinzolamide (JAN/USP/INN); (+)-4-ETHYLAMINO-3,4-DIHYDRO-2-(METHOXY)PROPYL-2H-THIENO[3,2-E]-1,2-THIAZINE-6-SULFONAMIDE-1,1-DIOXIDE; (4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide; (4R)-4-(ethylamino)-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide; (R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno(3,2-e)-1,2-thiazine-6-sulfonamide 1,1-dioxide; (R)-4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno(3,2-e)-1,2-thiazine-6-sulfonamide; 2H-Thieno(3,2-e)-1,2-thiazine-6-sulfonamide,4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-,1,1-dioxide,R

Indication

Disease Entry	ICD 11	Status	REF
Open-angle glaucoma	9C61	Approved	[1], [2]

Therapeutic Class

Antiglaucomic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

383.5

Topological Polar Surface Area (xlogp)

-0.3

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

9

ADMET Property

Absorption: The drug is absorbed into systemic circulation following topical ocular application [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 111 days [4]
Metabolism: The drug is metabolized via ophthalmic [3]

Chemical Identifiers

Formula: C12H21N3O5S3
IUPAC Name: (4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide
Canonical SMILES: CCN[C@H]1CN(S(=O)(=O)C2=C1C=C(S2)S(=O)(=O)N)CCCOC
InChI: InChI=1S/C12H21N3O5S3/c1-3-14-10-8-15(5-4-6-20-2)23(18,19)12-9(10)7-11(21-12)22(13,16)17/h7,10,14H,3-6,8H2,1-2H3,(H2,13,16,17)/t10-/m0/s1
InChIKey: HCRKCZRJWPKOAR-JTQLQIEISA-N

Cross-matching ID

PubChem CID: 68844
ChEBI ID: CHEBI:3176
CAS Number: 138890-62-7
DrugBank ID: DB01194
TTD ID: D01MUR
INTEDE ID: DR0229

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase IV (CA-IV)	TTZHA0O	CAH4_HUMAN	Modulator	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Open-angle glaucoma

ICD Disease Classification

9C61

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Carbonic anhydrase IV (CA-IV)	DTT	CA4	1.58E-77	-2.02	-1.77
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.87E-03	-6.67E-02	-2.12E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Brinzolamide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Choline salicylate	DM8P137	Major	Increased plasma concentration of Brinzolamide and Choline salicylate due to competitive binding of plasma proteins.	Postoperative inflammation [1A00-CA43]	[24]
Salsalate	DM13P4C	Major	Increased plasma concentration of Brinzolamide and Salsalate due to competitive binding of plasma proteins.	Rheumatoid arthritis [FA20]	[24]
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References

1	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).
2	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
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4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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8	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
9	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
10	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
11	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
12	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
13	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
14	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
15	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
16	Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8.
17	Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1149-54.
18	Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
19	Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
20	Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-r... Bioorg Med Chem Lett. 2008 Aug 1;18(15):4282-6.
21	Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates. Bioorg Med Chem Lett. 2005 Feb 1;15(3):573-8.
22	Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mamm... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3601-5.
23	Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22.
24	Cowan RA, Hartnell GG, Lowdell CP, Baird IM, Leak AM "Metabolic acidosis induced by carbonic anhydrase inhibitors and salicylates in patients with normal renal function." Br Med J (Clin Res Ed) 289 (1984): 347-8. [PMID: 6432091]