Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOGC15N)

• DOT Name: Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2)
• Synonyms: Gamma-GCG 2; EC 4.3.2.7; Cation transport regulator-like protein 2
• Gene Name: CHAC2
• UniProt ID: CHAC2_HUMAN
• PDB ID: 6K95; 6KY0; 6KY1
• EC Number: 4.3.2.7
• Pfam ID: PF04752
• Sequence:
  MWVFGYGSLIWKVDFPYQDKLVGYITNYSRRFWQGSTDHRGVPGKPGRVVTLVEDPAGCV
  WGVAYRLPVGKEEEVKAYLDFREKGGYRTTTVIFYPKDPTTKPFSVLLYIGTCDNPDYLG
  PAPLEDIAEQIFNAAGPSGRNTEYLFELANSIRNLVPEEADEHLFALEKLVKERLEGKQN
  LNCI
• Function: Catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glutathione synthesis and recycling (R-HSA-174403)
• BioCyc Pathway: MetaCyc:ENSG00000143942-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[15]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[13]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[7]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[22]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Glutathione-specific gamma-glutamylcyclotransferase 2 (CHAC2).	[9]

References

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• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [16] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
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• [20] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.