Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMBAPFG)

• Drug Name: Brinzolamide Drug Info
• 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
Ocular hypertension	9C61.01	Approved	[1]
Open-angle glaucoma	9C61	Approved	[2]

• Therapeutic Class: Antiglaucomic Agents
• Cross-matching ID:
  PubChem CID: 68844
  ChEBI ID: CHEBI:3176
  CAS Number: CAS 138890-62-7
  TTD Drug ID: DMBAPFG
  INTEDE Drug ID: DR0229

Molecule-Related Drug Atlas

Drug(s) Targeting Carbonic anhydrase IV (CA-IV)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[6]
Sulfamylon	DMIO1K0	Bacterial infection	1A00-1C4Z	Approved	[7]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
PARABEN	DMEW5Z8	N. A.	N. A.	Phase 3	[9]
PHENOL	DM1QSM3	N. A.	N. A.	Phase 2/3	[8]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[10]
Sodium pyruvate	DMST6A3	Asthma	CA23	Phase 1/2	[11]
SULFAMIDE	DMMAS3K	N. A.	N. A.	Phase 1	[12]
FERULIC ACID	DMJC7NF	Discovery agent	N.A.	Patented	[9]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

Drug(s) Affected By HLA class I histocompatibility antigen, B alpha chain (HLA-B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[23]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[24]
Allopurinol	DMLPAOB	Gout	FA25	Approved	[25]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[28]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[5]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[29]
Flucloxacillin	DMNUWST	Bacterial infection	1A00-1C4Z	Approved	[30]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[31]

Drug(s) Affected By HLA class I histocompatibility antigen, A alpha chain (HLA-A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[32]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[24]
Allopurinol	DMLPAOB	Gout	FA25	Approved	[33]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[34]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[31]
Ticlopidine	DMO946V	Acute coronary syndrome	BA41	Approved	[35]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[31]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[36]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[5]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[5]

Drug(s) Affected By Rho GTPase-activating protein 45 (ARHGAP45)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[5]
Acetazolamide	DM1AF5U	Absence epilepsy		Approved	[5]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[37]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[38]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Indapamide	DMGN1PW	Edema	MG29	Approved	[5]
Cefepime	DMHVWIK	Bacterial infection	1A00-1C4Z	Approved	[5]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[39]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[40]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[41]

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	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Gene/Protein Processing	[5]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Gene/Protein Processing	[5]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Gene/Protein Processing	[5]

References

• [1] Brinzolamide FDA Label
• [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: 6797).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] 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.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] 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.
• [19] 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.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] 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.
• [22] 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.
• [23] Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008 Oct;9(10):1543-6. doi: 10.2217/14622416.9.10.1543.
• [24] Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010 Mar;11(3):349-56. doi: 10.2217/pgs.09.162.
• [25] HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4134-9. doi: 10.1073/pnas.0409500102. Epub 2005 Mar 2.
• [26] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [27] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [28] HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013 Jul;54(7):1307-14. doi: 10.1111/epi.12217. Epub 2013 May 20.
• [29] Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002 Mar 30;359(9312):1121-2. doi: 10.1016/S0140-6736(02)08158-8.
• [30] HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009 Jul;41(7):816-9. doi: 10.1038/ng.379. Epub 2009 May 31.
• [31] HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PLoS One. 2013 Jul 9;8(7):e68111. doi: 10.1371/journal.pone.0068111. Print 2013.
• [32] HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011 Mar 24;364(12):1134-43. doi: 10.1056/NEJMoa1013297.
• [33] Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011 May;21(5):303-7. doi: 10.1097/FPC.0b013e32834282b8.
• [34] A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. Int J Immunogenet. 2011 Aug;38(4):303-9. doi: 10.1111/j.1744-313X.2011.01011.x. Epub 2011 May 4.
• [35] Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J. 2008 Feb;8(1):29-33. doi: 10.1038/sj.tpj.6500442. Epub 2007 Mar 6.
• [36] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [37] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [38] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [39] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [40] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [41] Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy. Blood. 2009 Mar 19;113(12):2715-22. doi: 10.1182/blood-2008-05-158956. Epub 2008 Dec 18.