Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVG296F)

• DOT Name: 6-phosphogluconate dehydrogenase, decarboxylating (PGD)
• Synonyms: EC 1.1.1.44
• Gene Name: PGD
• UniProt ID: 6PGD_HUMAN
• PDB ID: 2JKV; 4GWG; 4GWK; 5UQ9
• EC Number: 1.1.1.44
• Pfam ID: PF00393 ; PF03446
• Sequence:
  MAQADIALIGLAVMGQNLILNMNDHGFVVCAFNRTVSKVDDFLANEAKGTKVVGAQSLKE
  MVSKLKKPRRIILLVKAGQAVDDFIEKLVPLLDTGDIIIDGGNSEYRDTTRRCRDLKAKG
  ILFVGSGVSGGEEGARYGPSLMPGGNKEAWPHIKTIFQGIAAKVGTGEPCCDWVGDEGAG
  HFVKMVHNGIEYGDMQLICEAYHLMKDVLGMAQDEMAQAFEDWNKTELDSFLIEITANIL
  KFQDTDGKHLLPKIRDSAGQKGTGKWTAISALEYGVPVTLIGEAVFARCLSSLKDERIQA
  SKKLKGPQKFQFDGDKKSFLEDIRKALYASKIISYAQGFMLLRQAATEFGWTLNYGGIAL
  MWRGGCIIRSVFLGKIKDAFDRNPELQNLLLDDFFKSAVENCQDSWRRAVSTGVQAGIPM
  PCFTTALSFYDGYRHEMLPASLIQAQRDYFGAHTYELLAKPGQFIHTNWTGHGGTVSSSS
  YNA
• Function: Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway:
  NFE2L2 regulates pentose phosphate pathway genes (R-HSA-9818028)
  Pentose phosphate pathway (R-HSA-71336)
• BioCyc Pathway: MetaCyc:HS06949-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 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[1]

28 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-phosphogluconate dehydrogenase, decarboxylating (PGD).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
Methylene blue	DMJAPE7	Approved	Methylene blue increases the activity of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[12]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[13]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[3]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[15]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
Ferulic Acid	DMJC7NF	Patented	Ferulic Acid decreases the activity of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[17]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the activity of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[14]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[18]
Chrysin	DM7V2LG	Investigative	Chrysin decreases the activity of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[14]
methyl salicylate	DMKCG8H	Investigative	methyl salicylate increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]
2-Propanol, Isopropanol	DML5O0H	Investigative	2-Propanol, Isopropanol increases the expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD).	[10]

References

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• [9] 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.
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• [11] Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. J Lab Clin Med. 1991 Apr;117(4):325-31.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [14] Investigation of the effects of some phenolic compounds on the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from human erythrocytes. J Biochem Mol Toxicol. 2014 Nov;28(11):510-4. doi: 10.1002/jbt.21592. Epub 2014 Aug 6.
• [15] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [16] 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.
• [17] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [18] Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009 Feb 12;177(3):173-80. doi: 10.1016/j.cbi.2008.10.051. Epub 2008 Nov 6.