Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT300SMK)

• DOT Name: Glucose-6-phosphate 1-dehydrogenase (G6PD)
• Synonyms: G6PD; EC 1.1.1.49
• Gene Name: G6PD
• Related Disease:
  Anemia, nonspherocytic hemolytic, due to G6PD deficiency
  G6PD deficiency
  Obsolete class I glucose-6-phosphate dehydrogenase deficiency
• UniProt ID: G6PD_HUMAN
• PDB ID: 1QKI; 2BH9; 2BHL; 5UKW; 6E07; 6E08; 6JYU; 6VA0; 6VA7; 6VA8; 6VA9; 6VAQ; 7SEH; 7SEI; 7SNF; 7SNG; 7SNH; 7SNI; 7TOE; 7TOF; 7UAG; 7UAL; 7UC2; 7ZVD
• EC Number: 1.1.1.49
• Pfam ID: PF02781 ; PF00479
• Sequence:
  MAEQVALSRTQVCGILREELFQGDAFHQSDTHIFIIMGASGDLAKKKIYPTIWWLFRDGL
  LPENTFIVGYARSRLTVADIRKQSEPFFKATPEEKLKLEDFFARNSYVAGQYDDAASYQR
  LNSHMNALHLGSQANRLFYLALPPTVYEAVTKNIHESCMSQIGWNRIIVEKPFGRDLQSS
  DRLSNHISSLFREDQIYRIDHYLGKEMVQNLMVLRFANRIFGPIWNRDNIACVILTFKEP
  FGTEGRGGYFDEFGIIRDVMQNHLLQMLCLVAMEKPASTNSDDVRDEKVKVLKCISEVQA
  NNVVLGQYVGNPDGEGEATKGYLDDPTVPRGSTTATFAAVVLYVENERWDGVPFILRCGK
  ALNERKAEVRLQFHDVAGDIFHQQCKRNELVIRVQPNEAVYTKMMTKKPGMFFNPEESEL
  DLTYGNRYKNVKLPDAYERLILDVFCGSQMHFVRSDELREAWRIFTPLLHQIELEKPKPI
  PYIYGSRGPTEADELMKRVGFQYEGTYKWVNPHKL
• Function: Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis.
• Tissue Specificity: Isoform Long is found in lymphoblasts, granulocytes and sperm.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Central carbon metabolism in cancer (hsa05230)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Pentose phosphate pathway (R-HSA-71336)
  NFE2L2 regulates pentose phosphate pathway genes (R-HSA-9818028)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
• BioCyc Pathway: MetaCyc:HS08467-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anemia, nonspherocytic hemolytic, due to G6PD deficiency	DISYJ2T2	Definitive	X-linked	[1]
G6PD deficiency	DISYF1GO	Definitive	X-linked	[1]
Obsolete class I glucose-6-phosphate dehydrogenase deficiency	DISZK9PK	Supportive	X-linked	[2]

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cyclophosphamide	DM4O2Z7	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) increases the Haemolytic anaemia ADR of Cyclophosphamide.	[46]
Ciprofloxacin XR	DM2NLS9	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) increases the response to substance of Ciprofloxacin XR.	[47]
Primaquine	DMWQ16I	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) decreases the response to substance of Primaquine.	[48]
Glibenclamide	DM8JXPZ	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) increases the Haemolysis ADR of Glibenclamide.	[46]
Teniposide	DMLW57T	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) increases the Cytogenetic abnormality ADR of Teniposide.	[46]
Dapsone	DM4LT8A	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) increases the response to substance of Dapsone.	[49]
Isosorbide dinitrate	DMBI4JG	Approved	Glucose-6-phosphate 1-dehydrogenase (G6PD) decreases the response to substance of Isosorbide dinitrate.	[50]

4 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 Glucose-6-phosphate 1-dehydrogenase (G6PD).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[33]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[37]

55 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 Glucose-6-phosphate 1-dehydrogenase (G6PD).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[15]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[17]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[18]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[19]
Aspirin	DM672AH	Approved	Aspirin decreases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[20]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[17]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[5]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[17]
Isoniazid	DM5JVS3	Approved	Isoniazid decreases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[23]
Clavulanate	DM2FGRT	Approved	Clavulanate increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[24]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
Aluminium	DM6ECN9	Approved	Aluminium increases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[25]
Hesperidin	DMI5DW1	Approved	Hesperidin decreases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[26]
Methylene blue	DMJAPE7	Approved	Methylene blue increases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[27]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[28]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[26]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[29]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[14]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[30]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[31]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[34]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[36]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
Ferulic Acid	DMJC7NF	Patented	Ferulic Acid decreases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[38]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[39]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[40]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[41]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[42]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[43]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[5]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the activity of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[26]
methyl salicylate	DMKCG8H	Investigative	methyl salicylate increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
2-Propanol, Isopropanol	DML5O0H	Investigative	2-Propanol, Isopropanol increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[21]
DZNep	DM0JXBK	Investigative	DZNep decreases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[44]
Genistein-7-glucoside	DMMLNTW	Investigative	Genistein-7-glucoside increases the expression of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Glucose-6-phosphate 1-dehydrogenase (G6PD).	[22]

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