Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT25JBA3)

• DOT Name: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3)
• Synonyms: 6PF-2-K/Fru-2,6-P2ase 3; PFK/FBPase 3; 6PF-2-K/Fru-2,6-P2ase brain/placenta-type isozyme; Renal carcinoma antigen NY-REN-56; iPFK-2
• Gene Name: PFKFB3
• UniProt ID: F263_HUMAN
• PDB ID: 2AXN; 2DWO; 2DWP; 2I1V; 3QPU; 3QPV; 3QPW; 4D4J; 4D4K; 4D4L; 4D4M; 4MA4; 5AJV; 5AJW; 5AJX; 5AJY; 5AJZ; 5AK0; 6ETJ; 6HVH; 6HVI; 6HVJ; 6IBX; 6IBY; 6IBZ; 6IC0
• EC Number: 2.7.1.105; 3.1.3.46
• Pfam ID: PF01591 ; PF00300
• Sequence:
  MPLELTQSRVQKIWVPVDHRPSLPRSCGPKLTNSPTVIVMVGLPARGKTYISKKLTRYLN
  WIGVPTKVFNVGEYRREAVKQYSSYNFFRPDNEEAMKVRKQCALAALRDVKSYLAKEGGQ
  IAVFDATNTTRERRHMILHFAKENDFKAFFIESVCDDPTVVASNIMEVKISSPDYKDCNS
  AEAMDDFMKRISCYEASYQPLDPDKCDRDLSLIKVIDVGRRFLVNRVQDHIQSRIVYYLM
  NIHVQPRTIYLCRHGENEHNLQGRIGGDSGLSSRGKKFASALSKFVEEQNLKDLRVWTSQ
  LKSTIQTAEALRLPYEQWKALNEIDAGVCEELTYEEIRDTYPEEYALREQDKYYYRYPTG
  ESYQDLVQRLEPVIMELERQENVLVICHQAVLRCLLAYFLDKSAEEMPYLKCPLHTVLKL
  TPVAYGCRVESIYLNVESVCTHRERSEDAKKGPNPLMRRNSVTPLASPEPTKKPRINSFE
  EHVASTSAALPSCLPPEVPTQLPGQNMKGSRSSADSSRKH
• Function: Catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Fructose and mannose metabolism (hsa00051)
  Metabolic pathways (hsa01100)
  HIF-1 sig.ling pathway (hsa04066)
  AMPK sig.ling pathway (hsa04152)
• Reactome Pathway: Regulation of glycolysis by fructose 2,6-bisphosphate metabolism (R-HSA-9634600)
• BioCyc Pathway: MetaCyc:HS10144-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
Bevacizumab	DMSD1UN	Approved	6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) increases the Hypertension ADR of Bevacizumab.	[31]

5 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-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[20]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[27]

32 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 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[12]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[13]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[14]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[15]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[15]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[17]
GSK525762	DMPAWBN	Phase 1	GSK525762 increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[23]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[24]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[25]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[26]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[8]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[28]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[29]
I-BET151	DMYRUH2	Investigative	I-BET151 increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[18]
2-(carboxymethylamino)-2-oxoacetic acid	DMQ2SNL	Investigative	2-(carboxymethylamino)-2-oxoacetic acid increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).	[30]

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