Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO6C0IQ)

• DOT Name: 6-phosphogluconolactonase (PGLS)
• Synonyms: 6PGL; EC 3.1.1.31
• Gene Name: PGLS
• Related Disease:
  Breast cancer
  Breast carcinoma
  Osteoporosis
  Malaria
• UniProt ID: 6PGL_HUMAN
• EC Number: 3.1.1.31
• Pfam ID: PF01182
• Sequence:
  MAAPAPGLISVFSSSQELGAALAQLVAQRAACCLAGARARFALGLSGGSLVSMLARELPA
  AVAPAGPASLARWTLGFCDERLVPFDHAESTYGLYRTHLLSRLPIPESQVITINPELPVE
  EAAEDYAKKLRQAFQGDSIPVFDLLILGVGPDGHTCSLFPDHPLLQEREKIVAPISDSPK
  PPPQRVTLTLPVLNAARTVIFVATGEGKAAVLKRILEDQEENPLPAALVQPHTGKLCWFL
  DEAAARLLTVPFEKHSTL
• Function: Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway: Pentose phosphate pathway (R-HSA-71336)
• BioCyc Pathway: MetaCyc:HS05370-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Osteoporosis	DISF2JE0	Strong	Biomarker	[2]
Malaria	DISQ9Y50	Limited	Altered Expression	[3]

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 6-phosphogluconolactonase (PGLS).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 6-phosphogluconolactonase (PGLS).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 6-phosphogluconolactonase (PGLS).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 6-phosphogluconolactonase (PGLS).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 6-phosphogluconolactonase (PGLS).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 6-phosphogluconolactonase (PGLS).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of 6-phosphogluconolactonase (PGLS).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of 6-phosphogluconolactonase (PGLS).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of 6-phosphogluconolactonase (PGLS).	[12]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of 6-phosphogluconolactonase (PGLS).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 6-phosphogluconolactonase (PGLS).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 6-phosphogluconolactonase (PGLS).	[15]

References

• [1] Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer.Dis Markers. 2018 Feb 25;2018:9369358. doi: 10.1155/2018/9369358. eCollection 2018.
• [2] Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density.Proteomics. 2008 Oct;8(20):4259-72. doi: 10.1002/pmic.200700480.
• [3] Expression of Plasmodium falciparum G6PD-6PGL in laboratory parasites and in patient isolates in G6PD-deficient and normal Nigerian children.Br J Haematol. 2003 Aug;122(4):662-8. doi: 10.1046/j.1365-2141.2003.04397.x.
• [4] 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.
• [5] 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.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] [Differential proteomic expression in human liver cells stimulated by hydroquinone]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2006 Nov;24(11):658-61.
• [12] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [13] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.