Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3VM4JX)

• DOT Name: Phosphoglucomutase-1 (PGM1)
• Synonyms: PGM 1; EC 5.4.2.2; Glucose phosphomutase 1
• Gene Name: PGM1
• Related Disease: PGM1-congenital disorder of glycosylation
• UniProt ID: PGM1_HUMAN
• PDB ID: 5EPC; 5F9C; 5HSH; 5JN5; 5TR2; 5VBI; 5VEC; 5VG7; 5VIN; 6SNO; 6SNP; 6SNQ; 6UIQ; 6UO6; 7S0W; 7S77
• EC Number: 5.4.2.2
• Pfam ID: PF02878 ; PF02879 ; PF02880
• Sequence:
  MVKIVTVKTQAYQDQKPGTSGLRKRVKVFQSSANYAENFIQSIISTVEPAQRQEATLVVG
  GDGRFYMKEAIQLIARIAAANGIGRLVIGQNGILSTPAVSCIIRKIKAIGGIILTASHNP
  GGPNGDFGIKFNISNGGPAPEAITDKIFQISKTIEEYAVCPDLKVDLGVLGKQQFDLENK
  FKPFTVEIVDSVEAYATMLRSIFDFSALKELLSGPNRLKIRIDAMHGVVGPYVKKILCEE
  LGAPANSAVNCVPLEDFGGHHPDPNLTYAADLVETMKSGEHDFGAAFDGDGDRNMILGKH
  GFFVNPSDSVAVIAANIFSIPYFQQTGVRGFARSMPTSGALDRVASATKIALYETPTGWK
  FFGNLMDASKLSLCGEESFGTGSDHIREKDGLWAVLAWLSILATRKQSVEDILKDHWQKY
  GRNFFTRYDYEEVEAEGANKMMKDLEALMFDRSFVGKQFSANDKVYTVEKADNFEYSDPV
  DGSISRNQGLRLIFTDGSRIVFRLSGTGSAGATIRLYIDSYEKDVAKINQDPQVMLAPLI
  SIALKVSQLQERTGRTAPTVIT
• Function: This enzyme participates in both the breakdown and synthesis of glucose.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Pentose phosphate pathway (hsa00030)
  Galactose metabolism (hsa00052)
  Purine metabolism (hsa00230)
  Starch and sucrose metabolism (hsa00500)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway:
  Defective PGM1 causes PGM1-CDG (R-HSA-5609974)
  Neutrophil degranulation (R-HSA-6798695)
  Glycogen breakdown (glycogenolysis) (R-HSA-70221)
  Galactose catabolism (R-HSA-70370)
  Glycogen synthesis (R-HSA-3322077)
• BioCyc Pathway: MetaCyc:HS01335-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
PGM1-congenital disorder of glycosylation	DISFFUBJ	Definitive	Autosomal recessive	[1]

28 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 Phosphoglucomutase-1 (PGM1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphoglucomutase-1 (PGM1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphoglucomutase-1 (PGM1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphoglucomutase-1 (PGM1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phosphoglucomutase-1 (PGM1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphoglucomutase-1 (PGM1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phosphoglucomutase-1 (PGM1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Phosphoglucomutase-1 (PGM1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Phosphoglucomutase-1 (PGM1).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Phosphoglucomutase-1 (PGM1).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Phosphoglucomutase-1 (PGM1).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Phosphoglucomutase-1 (PGM1).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Phosphoglucomutase-1 (PGM1).	[14]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Phosphoglucomutase-1 (PGM1).	[15]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Phosphoglucomutase-1 (PGM1).	[16]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Phosphoglucomutase-1 (PGM1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phosphoglucomutase-1 (PGM1).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phosphoglucomutase-1 (PGM1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phosphoglucomutase-1 (PGM1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phosphoglucomutase-1 (PGM1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phosphoglucomutase-1 (PGM1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Phosphoglucomutase-1 (PGM1).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phosphoglucomutase-1 (PGM1).	[23]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Phosphoglucomutase-1 (PGM1).	[24]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Phosphoglucomutase-1 (PGM1).	[25]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Phosphoglucomutase-1 (PGM1).	[26]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Phosphoglucomutase-1 (PGM1).	[16]
Alpha-naphthoflavone	DMELOIQ	Investigative	Alpha-naphthoflavone increases the expression of Phosphoglucomutase-1 (PGM1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Phosphoglucomutase-1 (PGM1).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Phosphoglucomutase-1 (PGM1).	[20]

References

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• [7] 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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• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [16] Linalool is a PPARalpha ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J Lipid Res. 2014 Jun;55(6):1098-110.
• [17] Capsaicin induced the upregulation of transcriptional and translational expression of glycolytic enzymes related to energy metabolism in human intestinal epithelial cells. J Agric Food Chem. 2009 Dec 9;57(23):11148-53.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [22] 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.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [25] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [26] 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation. Toxicol Sci. 2013 Mar;132(1):235-49.