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

General Information of Drug (ID: DM1AF5U)

• Drug Name: Acetazolamide Drug Info
• Synonyms: Acetadiazol; Acetamidothiadiazolesulfonamide; Acetamox; Acetazolam; Acetazolamid; Acetazolamida; Acetazolamidum; Acetazolamine; Acetazoleamide; Acetozalamide; AkZol; ApoAcetazolamide; Atenezol; Cidamex; Dazamide; Defiltran; Dehydratin; Diacarb; Diakarb; Diamox; Didoc; Diluran; Diuramid; Diuramide; Diuriwas; Diutazol; Donmox; Duiramid; Edemox; Eumicton; Fonurit; Glauconox; Glaumox; Glaupax; Glupax; HumaZolamide; Natrionex; Nephramid; Nephramide; Phonurit; Storzolamide; Vetamox; Acetazolamide Apotex Brand; Acetazolamide Chiesi Brand; Acetazolamide Dioptic Brand; Acetazolamide Grin Brand; Acetazolamide ICN Brand; Acetazolamide Jumer Brand; Acetazolamide Llorens Brand; Acetazolamide Medphano Brand; Acetazolamide Novopharm Brand; Acetazolamide Orion Brand; Acetazolamide Wassermann Brand; Ak Zol; Apo Acetazolamide; Apotex Brand of Acetazolamide; Chiesi Brand of Acetazolamide; Ciba Vision Brand of Acetazolamide; DiamoxSequels; Dioptic Brand of Acetazolamide; Grin Brand of Acetazolamide; Huma Zolamide; ICN Brand of Acetazolamide; Jumer Brand of Acetazolamide; Llorens Brand of Acetazolamide; Medphano Brand of Acetazolamide; Monosodium Salt Acetazolamide; Novopharm Brand of Acetazolamide; Orion Brand of Acetazolamide; Storz Brand of Acetazolamide Preparation; Wassermann Brand of Acetazolamide; Wyeth Brand of Acetazolamide Preparation; A 6011; Carbonic anhydrase inhibitor 6063; Acetazolamida [INN-Spanish]; Acetazolamide (AAZ); Acetazolamide, Monosodium Salt; Acetazolamidum [INN-Latin]; Ak-Zol; Apo-Acetazolamide; Carbonic Anhydrase Inhibitor No. 6063; Diamox (TN); Diureticum-holzinger; Huma-Zolamide; SK-acetazolamide; Acetazolamide Sodium, (Sterile); Acetazolamide [INN:BAN:JAN]; Acetazolamide (JP15/USP/INN); 4-Diamox

Indication

Disease Entry	ICD 11	Status	REF
Absence epilepsy		Approved	[1]
Altitude sickness		Approved	[1]
Edema	MG29	Approved	[1]
Glaucoma/ocular hypertension	9C61	Approved	[2]

• Therapeutic Class: Anticonvulsants
• Cross-matching ID:
  PubChem CID: 1986
  ChEBI ID: CHEMBL20
  CAS Number: CAS 59-66-5
  TTD Drug ID: DM1AF5U
  VARIDT Drug ID: DR00606
  ACDINA Drug ID: D00010

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[8]
Ethoxzolamide	DMVO4ED	Glaucoma/ocular hypertension	9C61	Approved	[3]
Dichlorphenamide	DMH7IDQ	Chronic glaucoma	9C61.0Z	Approved	[3]
Methazolamide	DM7J2TA	Glaucoma/ocular hypertension	9C61	Approved	[9]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
PARABEN	DMEW5Z8	N. A.	N. A.	Phase 3	[11]
CG-100649	DMIKMA9	Arthritis	FA20	Phase 3	[12]
PHENOL	DM1QSM3	N. A.	N. A.	Phase 2/3	[10]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[13]
SULFAMIDE	DMMAS3K	N. A.	N. A.	Phase 1	[14]

Drug(s) Affected By Carbonic anhydrase 12 (CA12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[17]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[18]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[15]
Topiramate	DM82Z30	Alcohol dependence	6C40.2	Approved	[19]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[20]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Mestranol	DMG3F94	Contraception	QA21	Approved	[15]

Drug(s) Affected By Carbonic anhydrase 9 (CA9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[23]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[25]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[27]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[28]
Bortezomib	DMNO38U	Leukemia		Approved	[29]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[30]
Amphotericin B	DMTAJQE	Acne vulgaris	ED80	Approved	[31]

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	[6]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[32]
Brinzolamide	DMBAPFG	Ocular hypertension	9C61.01	Approved	[6]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[33]
Indapamide	DMGN1PW	Edema	MG29	Approved	[6]
Cefepime	DMHVWIK	Bacterial infection	1A00-1C4Z	Approved	[6]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[28]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[34]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[35]

Drug(s) Affected By Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[26]
Paricalcitol	DMYBV3G	Hyperparathyroidism	5A51	Approved	[5]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[36]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[33]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[37]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[38]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[39]
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[40]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[5]
Furosemide	DMMQ8ZG	Congestive heart failure	BD10	Approved	[5]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase I (CA-I)	TTHQPL7	CAH1_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Carbonic anhydrase 12 (CA12)	OT6WNFU8	CAH12_HUMAN	Gene/Protein Processing	[4]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Gene/Protein Processing	[4]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Drug Response	[5]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Gene/Protein Processing	[6]
Uromodulin	OTHP6Y7F	UROM_HUMAN	Gene/Protein Processing	[7]

References

• [1] Acetazolamide 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: 6792).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase IX and XII inhibitors. J Med Chem. 2011 Oct 13;54(19):6905-18.
• [5] 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.
• [6] 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.
• [7] Tamm-Horsfall protein accumulation in glomeruli during acetazolamide-induced acute renal failure. Am J Nephrol. 1989;9(1):56-7. doi: 10.1159/000167936.
• [8] 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.
• [9] 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: 2597).
• [10] Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
• [11] 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.
• [12] Understanding the Dual Inhibition of COX-2 and Carbonic Anhydrase-II by Celecoxib and CG100649 Using Density Functional Theory Calculations and other Molecular Modelling Approaches. Protein Pept Lett. 2015;22(10):903-12.
• [13] 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.
• [14] Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme XIII with anions. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5435-9.
• [15] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [16] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [17] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Design, synthesis, and biological evaluation of novel carbohydrate-based sulfamates as carbonic anhydrase inhibitors. J Med Chem. 2011 Mar 10;54(5):1481-9.
• [20] DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. Physiol Genomics. 2004 Apr 13;17(2):122-9. doi: 10.1152/physiolgenomics.00002.2003.
• [21] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [22] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [23] NO-sulindac inhibits the hypoxia response of PC-3 prostate cancer cells via the Akt signalling pathway. Int J Cancer. 2009 Jan 1;124(1):223-32. doi: 10.1002/ijc.23934.
• [24] Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line. Neurochem Res. 2012 Feb;37(2):370-80. doi: 10.1007/s11064-011-0620-1. Epub 2011 Oct 4.
• [25] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [26] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [27] 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.
• [28] 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.
• [29] A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer. Clin Cancer Res. 2005 Aug 1;11(15):5526-33. doi: 10.1158/1078-0432.CCR-05-0081.
• [30] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [31] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [37] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [38] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [39] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [40] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.