Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPD9TDR)

• DOT Name: Zinc-alpha-2-glycoprotein (AZGP1)
• Synonyms: Zn-alpha-2-GP; Zn-alpha-2-glycoprotein
• Gene Name: AZGP1
• UniProt ID: ZA2G_HUMAN
• PDB ID: 1T7V; 1T7W; 1T7X; 1T7Y; 1T7Z; 1T80; 1ZAG; 3ES6; 6R2U
• Pfam ID: PF07654 ; PF00129
• Sequence:
  MVRMVPVLLSLLLLLGPAVPQENQDGRYSLTYIYTGLSKHVEDVPAFQALGSLNDLQFFR
  YNSKDRKSQPMGLWRQVEGMEDWKQDSQLQKAREDIFMETLKDIVEYYNDSNGSHVLQGR
  FGCEIENNRSSGAFWKYYYDGKDYIEFNKEIPAWVPFDPAAQITKQKWEAEPVYVQRAKA
  YLEEECPATLRKYLKYSKNILDRQDPPSVVVTSHQAPGEKKKLKCLAYDFYPGKIDVHWT
  RAGEVQEPELRGDVLHNGNGTYQSWVVVAVPPQDTAPYSCHVQHSSLAQPLVVPWEAS
• Function: Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids.
• Tissue Specificity: Blood plasma, seminal plasma, urine, saliva, sweat, epithelial cells of various human glands, liver.
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

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 decreases the methylation of Zinc-alpha-2-glycoprotein (AZGP1).	[1]

14 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 Zinc-alpha-2-glycoprotein (AZGP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[7]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[8]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[13]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Zinc-alpha-2-glycoprotein (AZGP1).	[15]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	D-glucose affects the secretion of Zinc-alpha-2-glycoprotein (AZGP1).	[14]

References

• [1] 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.
• [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] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [4] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [7] 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.
• [8] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [9] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [12] AZGP1 autoantibody predicts survival and histone deacetylase inhibitors increase expression in lung adenocarcinoma. J Thorac Oncol. 2008 Nov;3(11):1236-44. doi: 10.1097/JTO.0b013e318189f5ec.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Calorie restriction-induced changes in the secretome of human adipocytes, comparison with resveratrol-induced secretome effects. Biochim Biophys Acta. 2014 Sep;1844(9):1511-22. doi: 10.1016/j.bbapap.2014.04.023. Epub 2014 May 5.
• [15] 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.