Details of Drug Off-Target (DOT)

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

• DOT Name: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
• Synonyms: GAPDH; EC 1.2.1.12; Peptidyl-cysteine S-nitrosylase GAPDH; EC 2.6.99.-
• Gene Name: GAPDH
• UniProt ID: G3P_HUMAN
• PDB ID: 1U8F; 1ZNQ; 3GPD; 4WNC; 4WNI; 6ADE; 6IQ6; 6M61; 6YND; 6YNE; 6YNF; 6YNH; 8DNS; 8P5F
• EC Number: 1.2.1.12; 2.6.99.-
• Pfam ID: PF02800 ; PF00044
• Sequence:
  MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVYMFQYDSTHGKFHGTV
  KAENGKLVINGNPITIFQERDPSKIKWGDAGAEYVVESTGVFTTMEKAGAHLQGGAKRVI
  ISAPSADAPMFVMGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHA
  ITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTANV
  SVVDLTCRLEKPAKYDDIKKVVKQASEGPLKGILGYTEHQVVSSDFNSDTHSSTFDAGAG
  IALNDHFVKLISWYDNEFGYSNRVVDLMAHMASKE
• Function: Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  HIF-1 sig.ling pathway (hsa04066)
  Alzheimer disease (hsa05010)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS03433-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) increases the Liver injury ADR of Ethanol.	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the splicing of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the activity of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[12]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[13]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[14]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[15]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[1]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[18]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[19]
Mebendazole	DMO14SG	Approved	Mebendazole decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[28]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[29]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[30]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[31]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[32]
1,2-NAPHTHOQUINONE	DMYXELH	Investigative	1,2-NAPHTHOQUINONE decreases the activity of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[34]

3 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 Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[17]
Mercaptopurine	DMTM2IK	Approved	Mercaptopurine affects the localization of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[12]
Syringic Acid	DM802V7	Investigative	Syringic Acid increases the secretion of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).	[25]

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