Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNFBVVQ)

• DOT Name: Carbonic anhydrase 1 (CA1)
• Synonyms: EC 4.2.1.1; Carbonate dehydratase I; Carbonic anhydrase B; CAB; Carbonic anhydrase I; CA-I; Cyanamide hydratase CA1; EC 4.2.1.69
• Gene Name: CA1
• UniProt ID: CAH1_HUMAN
• PDB ID: 1AZM ; 1BZM ; 1CRM ; 1CZM ; 1HCB ; 1HUG ; 1HUH ; 1J9W ; 1JV0 ; 2CAB ; 2FOY ; 2FW4 ; 2IT4 ; 2NMX ; 2NN1 ; 2NN7 ; 3LXE ; 3W6H ; 3W6I ; 4WR7 ; 4WUP ; 4WUQ ; 5E2M ; 5GMM ; 6EVR ; 6EX1 ; 6F3B ; 6FAF ; 6FAG ; 6G3V ; 6HWZ ; 6I0J ; 6I0L ; 6SWM ; 6XZE ; 6XZO ; 6XZS ; 6XZX ; 6XZY ; 6Y00 ; 7PLF ; 7Q0D ; 7QOB ; 7ZL5
• EC Number: 4.2.1.1; 4.2.1.69
• Pfam ID: PF00194
• Sequence:
  MASPDWGYDDKNGPEQWSKLYPIANGNNQSPVDIKTSETKHDTSLKPISVSYNPATAKEI
  INVGHSFHVNFEDNDNRSVLKGGPFSDSYRLFQFHFHWGSTNEHGSEHTVDGVKYSAELH
  VAHWNSAKYSSLAEAASKADGLAVIGVLMKVGEANPKLQKVLDALQAIKTKGKRAPFTNF
  DPSTLLPSSLDFWTYPGSLTHPPLYESVTWIICKESISVSSEQLAQFRSLLSNVEGDNAV
  PMQHNNRPTQPLKGRTVRASF
• Function: Catalyzes the reversible hydration of carbon dioxide. Can hydrate cyanamide to urea.
• KEGG Pathway:
  Nitrogen metabolism (hsa00910)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Erythrocytes take up oxygen and release carbon dioxide (R-HSA-1247673)
  Reversible hydration of carbon dioxide (R-HSA-1475029)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Erythrocytes take up carbon dioxide and release oxygen (R-HSA-1237044)
• BioCyc Pathway: MetaCyc:HS05785-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Bicarbonate	DMT5E36	Investigative	Carbonic anhydrase 1 (CA1) increases the chemical synthesis of Bicarbonate.	[16]

18 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carbonic anhydrase 1 (CA1).	[1]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Carbonic anhydrase 1 (CA1).	[2]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the activity of Carbonic anhydrase 1 (CA1).	[3]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Carbonic anhydrase 1 (CA1).	[4]
Propofol	DMB4OLE	Approved	Propofol decreases the activity of Carbonic anhydrase 1 (CA1).	[5]
Phenylephrine	DMZHUO5	Approved	Phenylephrine decreases the activity of Carbonic anhydrase 1 (CA1).	[6]
Candesartan	DMRK8OT	Approved	Candesartan decreases the activity of Carbonic anhydrase 1 (CA1).	[7]
Voriconazole	DMAOL2S	Approved	Voriconazole decreases the activity of Carbonic anhydrase 1 (CA1).	[8]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the activity of Carbonic anhydrase 1 (CA1).	[5]
T83193	DMHO29Y	Patented	T83193 decreases the activity of Carbonic anhydrase 1 (CA1).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Carbonic anhydrase 1 (CA1).	[10]
Rutin	DMEHRAJ	Investigative	Rutin decreases the activity of Carbonic anhydrase 1 (CA1).	[11]
Irbesartan	DMTP1DC	Investigative	Irbesartan decreases the activity of Carbonic anhydrase 1 (CA1).	[7]
CHALCONE	DM16QTM	Investigative	CHALCONE decreases the activity of Carbonic anhydrase 1 (CA1).	[12]
PHENYLTHIOUREA	DMM1IAU	Investigative	PHENYLTHIOUREA decreases the activity of Carbonic anhydrase 1 (CA1).	[13]
Thiourea	DMUELHN	Investigative	Thiourea decreases the activity of Carbonic anhydrase 1 (CA1).	[14]
1,2,4-Triazole	DM73F5A	Investigative	1,2,4-Triazole decreases the activity of Carbonic anhydrase 1 (CA1).	[15]
2,6-di-t-butylphenol	DMY8LDT	Investigative	2,6-di-t-butylphenol decreases the activity of Carbonic anhydrase 1 (CA1).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carbonic anhydrase 1 (CA1).	[9]

References

• [1] 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.
• [2] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [3] Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action. Int J Clin Pharmacol Ther. 2001 Jun;39(6):265-70.
• [4] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [5] Carbonic anhydrase inhibitors. Inhibition of human erythrocyte isozymes I and II with a series of antioxidant phenols bioorg. Med Chem. 2009 Apr 15;17(8):3207-11.
• [6] Synephrine and phenylephrine act as -amylase, -glycosidase, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase enzymes inhibitors. J Biochem Mol Toxicol. 2017 Nov;31(11). doi: 10.1002/jbt.21973. Epub 2017 Aug 11.
• [7] The mechanism of action of angiotensin II is dependent on direct activation of vascular smooth muscle carbonic anhydrase I. Int J Clin Lab Res. 2000;30(3):119-25. doi: 10.1007/s005990070010.
• [8] Inhibition profiles of Voriconazole against acetylcholinesterase, -glycosidase, and human carbonic anhydrase I and II isoenzymes. J Biochem Mol Toxicol. 2019 Oct;33(10):e22385. doi: 10.1002/jbt.22385. Epub 2019 Sep 3.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Inhibition properties of some flavonoids on carbonic anhydrase I and II isoenzymes purified from human erythrocytes. J Biochem Mol Toxicol. 2017 Sep;31(9).
• [12] Comparison of the inhibitory potential towards carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase of chalcone and chalcone epoxide. J Biochem Mol Toxicol. 2019 Feb;33(2):e22240.
• [13] Synthesis, characterization, antioxidant, antidiabetic, anticholinergic, and antiepileptic properties of novel N-substituted tetrahydropyrimidines based on phenylthiourea. J Biochem Mol Toxicol. 2018 Dec;32(12):e22221.
• [14] Synthesis of new cyclic thioureas and evaluation of their metal-chelating activity, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibition profiles. J Biochem Mol Toxicol. 2017 Jul;31(7).
• [15] In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones-Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles. J Biochem Mol Toxicol. 2018 Oct 28:e22239.
• [16] Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36.