Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOIBEW7)

• DOT Name: Corticosteroid-binding globulin (SERPINA6)
• Synonyms: CBG; Serpin A6; Transcortin
• Gene Name: SERPINA6
• Related Disease: Corticosteroid-binding globulin deficiency
• UniProt ID: CBG_HUMAN
• PDB ID: 2VDX; 2VDY; 4BB2; 4C41; 4C49
• Pfam ID: PF00079
• Sequence:
  MPLLLYTCLLWLPTSGLWTVQAMDPNAAYVNMSNHHRGLASANVDFAFSLYKHLVALSPK
  KNIFISPVSISMALAMLSLGTCGHTRAQLLQGLGFNLTERSETEIHQGFQHLHQLFAKSD
  TSLEMTMGNALFLDGSLELLESFSADIKHYYESEVLAMNFQDWATASRQINSYVKNKTQG
  KIVDLFSGLDSPAILVLVNYIFFKGTWTQPFDLASTREENFYVDETTVVKVPMMLQSSTI
  SYLHDSELPCQLVQMNYVGNGTVFFILPDKGKMNTVIAALSRDTINRWSAGLTSSQVDLY
  IPKVTISGVYDLGDVLEEMGIADLFTNQANFSRITQDAQLKSSKVVHKAVLQLNEEGVDT
  AGSTGVTLNLTSKPIILRFNQPFIIMIFDHFTWSSLFLARVMNPV
• Function: Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
• Tissue Specificity: Plasma; synthesized in liver. Has also been identified in a number of glycocorticoid responsive cells.
• Reactome Pathway:
  Prednisone ADME (R-HSA-9757110)
  Glucocorticoid biosynthesis (R-HSA-194002)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Corticosteroid-binding globulin deficiency	DISYKJVZ	Strong	Autosomal recessive	[1]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Corticosteroid-binding globulin (SERPINA6) increases the transport of Progesterone.	[11]

9 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 Corticosteroid-binding globulin (SERPINA6).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Corticosteroid-binding globulin (SERPINA6).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Corticosteroid-binding globulin (SERPINA6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Corticosteroid-binding globulin (SERPINA6).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Corticosteroid-binding globulin (SERPINA6).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Corticosteroid-binding globulin (SERPINA6).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Corticosteroid-binding globulin (SERPINA6).	[8]
Mitotane	DMU1GX0	Approved	Mitotane increases the expression of Corticosteroid-binding globulin (SERPINA6).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Corticosteroid-binding globulin (SERPINA6).	[3]

2 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 Corticosteroid-binding globulin (SERPINA6).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Corticosteroid-binding globulin (SERPINA6).	[10]

References

• [1] Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension. J Clin Endocrinol Metab. 2001 Aug;86(8):3692-700. doi: 10.1210/jcem.86.8.7724.
• [2] 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.
• [3] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans. J Clin Endocrinol Metab. 2006 Jun;91(6):2165-70. doi: 10.1210/jc.2005-2157. Epub 2006 Mar 21.
• [6] 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.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Withaferin A: A potential selective glucocorticoid receptor modulator with anti-inflammatory effect. Food Chem Toxicol. 2023 Sep;179:113949. doi: 10.1016/j.fct.2023.113949. Epub 2023 Jul 17.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] Single nucleotide polymorphisms in the human corticosteroid-binding globulin promoter alter transcriptional activity. Sci China Life Sci. 2012 Aug;55(8):699-708. doi: 10.1007/s11427-012-4365-0. Epub 2012 Aug 30.