Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ILP2U)

• DOT Name: Carbonic anhydrase 3 (CA3)
• Synonyms: EC 4.2.1.1; Carbonate dehydratase III; Carbonic anhydrase III; CA-III
• Gene Name: CA3
• UniProt ID: CAH3_HUMAN
• PDB ID: 1Z93; 1Z97; 2HFW; 3UYN; 3UYQ
• EC Number: 4.2.1.1
• Pfam ID: PF00194
• Sequence:
  MAKEWGYASHNGPDHWHELFPNAKGENQSPVELHTKDIRHDPSLQPWSVSYDGGSAKTIL
  NNGKTCRVVFDDTYDRSMLRGGPLPGPYRLRQFHLHWGSSDDHGSEHTVDGVKYAAELHL
  VHWNPKYNTFKEALKQRDGIAVIGIFLKIGHENGEFQIFLDALDKIKTKGKEAPFTKFDP
  SCLFPACRDYWTYQGSFTTPPCEECIVWLLLKEPMTVSSDQMAKLRSLLSSAENEPPVPL
  VSNWRPPQPINNRVVRASFK
• Function: Reversible hydration of carbon dioxide.
• Tissue Specificity: Muscle specific.
• KEGG Pathway:
  Nitrogen metabolism (hsa00910)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Reversible hydration of carbon dioxide (R-HSA-1475029)

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 3 (CA3) increases the chemical synthesis of Bicarbonate.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Carbonic anhydrase 3 (CA3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carbonic anhydrase 3 (CA3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carbonic anhydrase 3 (CA3).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Carbonic anhydrase 3 (CA3).	[4]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Carbonic anhydrase 3 (CA3).	[5]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Carbonic anhydrase 3 (CA3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carbonic anhydrase 3 (CA3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carbonic anhydrase 3 (CA3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Carbonic anhydrase 3 (CA3).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] 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.
• [5] 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.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] 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.